Fired Professor Wins Key Victory In Free Speech Case Over Mask, Vaccine Policy

 A professor who was fired from the University of Southern Maine for challenging COVID-19 mandates has won a critical courtroom victory, after a district judge ruled that her First Amendment lawsuit against the institution can proceed.

Patricia Griffin, who says she was fired for asking valid questions about mask and vaccination policies on campus during the COVID-19 pandemic, was granted the narrow win after the university filed a motion to dismiss the case in part. US District Judge Jon Levy ruled that while Griffin's First Amendment claim can proceed, other charges were dismissed.

On Aug. 18, 2021, the University of Maine announced a mandatory mask policy. Six days later, Griffin took part in a luncheon meeting via Zoom, where the speaker was Glenn Cummings, president of the university. Griffin says Cummings wasn't wearing a mask at the time.

Later that day she sent an email to the Dean of the College of Management and Human Service, claiming that she had been following "science, data, and evidence" related to the pandemic. Griffin said in the email that she was "searching for anything that will support wearing a mask while indoors as well as vaccinating an entire school population as the optimal method for stopping the transmission of the virus. The reality is that my research has found no evidence to support these measures."

She attached a document to her email summarizing the results of her research, which did not find "any overwhelming support for the wearing of masks nor the mandating of vaccines, especially since the overall survival rate is 99.7 percent if infected with Covid. And finally, from a legal perspective, asking for my vaccination status is a violation of HIPAA (Health Insurance Portability and Accountability Act)."

She then met with the Dean in another Zoom meeting, in which she says she never refused to wear a mask, or violate university policy.

Then, her fall semester classes were canceled. In a subsequent disciplinary conference, she was allegedly told that she wouldn't be allowed to teach her courses 100% online unless she resigned an accepted a part-time position.

On Sept. 8, 2021, she received a letter from Cummings notifying her that she had been suspended, and the university had moved to terminate her. She says the letter falsely stated that she refused to comply with university policy and wouldn't wear a mask.

She was formally terminated on Sept. 22.

For those who enjoy deep legal dives Jonathan Turley opines further:

We now have a positive ruling for free speech out of the District of Maine where Chief Judge Jon Levy has ruled in favor of a professor terminated by the University of Southern Maine for questioning mask and vaccination policies.

Judge Levy’s decision in Griffin v. University of Maine System is balanced and fair. He does not offer a full-throated endorsement of the claim by Professor Patricia Griffin, but rules that she has a right to a trial on the free speech claim.

Here are the basic facts.

On August 18, 2021, the Chancellor of the University of Maine System announced a mandatory mask policy.  On August 24, University President Glenn Cummings held a a luncheon meeting via Zoom. Notably, Cummings was not wearing a mask. After the meeting, Griffin sent an email to the Dean of the College of Management and Human Service that read in part:

“I first want to say how much I love teaching at [the University of Southern Maine] as well as working with such a great faculty. It really has been the highlight of my career and I owe a lot to you for sticking with me. The reason for this email is because I have been following the science, data, and evidence regarding SARS-CoV-2 and searching for anything that will support wearing a mask while indoors as well as vaccinating an entire school population as the optimal method for stopping the transmission of the virus. The reality is that my research has found no evidence to support these measures. I wanted to share the information I gathered and relied upon when making my decision regarding these mandates before the start of classes next Monday to see that my decisions are science, evidence, and data based. However, I do not want to cause any issues, especially for you, if I come to campus on Monday morning to teach my one face to face class so I wanted to give you enough time.”

Griffin attached a letter addressed to the Dean on her own research and objections to the policies. She concluded:

“In conclusion, I have followed the science, data, and evidence and cannot find any overwhelming support for the wearing of masks nor the mandating of vaccines, especially since the overall survival rate is 99.7% if infected with Covid. And finally, from a legal perspective, asking for my vaccination status is a violation of HIPAA.

My expectation is the University of Southern Maine will appreciate a faculty member who embraces critical thinking and applies both inductive and deductive reasoning rather than emotions when making decisions. I am teaching three courses this fall, two online and one face to face. I welcome any evidence you can provide to the contrary of what I have found which will convince me that my conclusions about the efficacy of wearing a mask and vaccinating an entire population are wrong.”

What followed quickly went from bad to worse for Griffin, who met with the Dean and again asked for the data supporting the University’s Policy and vaccination requirement.  While universities attacked academics who questioned these policies as opposed to “the science,” they largely refused to share the basis for the policies.

Despite the firing or sanctioning of academics who questioned pandemic policies, many have recently admitted that the efficacy of masks (particularly the common surgical masks) were radically overstated and unsupported. Moreover, studies have shown that critics were right in claiming that natural immunities from prior bouts with Covid offered as good or better protection than the vaccine. Nevertheless, the media participated in the demonization of these experts who were disciplined at universities and denied key positions in their fields.

In this case, Griffin alleged that immediately following the Zoom meeting, her fall semester courses were removed from the fall class list. She still did not back down and continued to ask for the data. She alleged that school officials then told her that she would not be allowed to teach courses 100% online unless she resigned and accepted a part-time position. On September 8, 2021, Cummings sent a letter to Griffin suspending her and informing her that the University would be moving to terminate her employment. Griffin alleges that the letter falsely asserted that she had refused to comply with the policies and included other false assertions.

The issue for the court was whether Griffin was speaking as a public employee or as a citizen.

“The “threshold inquiry” to determine whether a public employee engaged in protected speech is “whether [the employee] spoke as a citizen on a matter of public concern.” O’Connell v. Marrero-Recio, 724 F.3d 117, 123 (1st Cir. 2013). If the answer is no, the employee has no First Amendment retaliation claim. If the answer is yes, then the possibility of a First Amendment claim arises. Garcetti v. Ceballos, 547 U.S. 410, 418 (2006). “In order to survive a motion to dismiss, a plaintiff need not conclusively establish that her speech was made as a citizen; ‘it is sufficient that the complaint alleges facts that plausibly set forth citizen speech.’” Cannell v. Corizon, LLC, No. 1:14-cv-405-NT, 2015 WL 8664209, at *8 (D. Me. Dec. 11, 2015) (quoting Decotiis v. Whittemore, 635 F.3d 22, 34-35 (1st Cir. 2011)).”

The court found that there were factors under the relevant tests that cut both ways on whether Griffin was speaking as an employee or a citizen. However, given the governing standard for review, JudgeLevy read this evidence in her favor and the right to a trial on free speech claims (though he curtailed other aspects of her complaint):

Here, Griffin has pleaded sufficient facts to make it more than merely possible that once fully developed, the facts will support the conclusion that although Griffin’s speech related to her official duties as a public employee, the subject matter of her speech pertained to a matter of great public concern and was outside the scope of her duties as a professor of marketing. Whether the same conclusion may be true after the parties have completed discovery is another matter for another day. “[I]t is entirely possible that additional facts might show” that Griffin is not entitled to the relief that she seeks, but “absent factual development, dismissal is unwarranted” at this stage….

Putting aside the merits for trial, what should be clear is that, if the underlying facts are proven, the university acted in an abusive and capricious manner. Faced with a dissenting faculty member, the school opted to seek her termination rather than defend its policies or allow a dialogue on these measures.

As a public university, the Maine legislature should take note of this case and the need to reinforce free speech protections in the system. The level of intolerance for opposing views alleged in this complaint is chilling. If these facts are proven, there were grounds for termination but it was not the termination of Professor Griffin.

https://www.zerohedge.com/political/fired-professor-wins-key-victory-free-speech-case-over-mask-vaccine-policy

Busing Illegal Immigrants To Blue America Is Working

 by Jarrett Stepman via The Epoch Times,

Republican border-state strategy to send illegal immigrants to Democrat-run cities and states is paying off.

On Thursday, New York Gov. Kathy Hochul sent a letter to President Joe Biden begging for federal aid. Importantly, she finally acknowledged where the problem is coming from.

“This is a financial burden the city and state are shouldering on behalf of the federal government,” Hochul, a fellow Democrat, said of the illegal immigrants pouring into New York.

“I cannot ask New Yorkers to pay for what is fundamentally a federal responsibility,” the governor wrote. “And I urge the federal government to take prompt and significant action today to meet its obligation to New York State.”

In a press conference following release of the letter, Hochul further complained about illegal immigrants released into the country by the Biden administration.

What happened to all are welcome, no exceptions?

This is an interesting pivot from the New York governor. Until now, Democrat politicians mostly have been unwilling to criticize the White House in any way on the border security issue, or even suggest that the Biden administration is where the problem originates.

If you want to know the reason for the sudden pivot, a new poll sheds light. The Siena College poll released Tuesday shows that New Yorkers are deeply discontented about the surge of illegal immigrants in their state and mostly blame Democrat leaders.

“New Yorkers—including huge majorities of Democrats, Republicans, independents, upstaters and downstaters—overwhelmingly say that the recent influx of migrants to New York is a serious problem for the state,” Siena College pollster Steven Greenberg said.

Now, this may seem meaningless in the sense that New York is unlikely to become a red state any time soon. But keep in mind that the crime issue didn’t just swing seats from Democrat to Republican in the 2022 midterm elections, it likely also gave the GOP overall control of the U.S. House of Representatives.

Discontent over lawless Democrat policies is much worse now, and New York voters are heaping the blame on Hochul, New York City Mayor Eric Adams, and, most of all, Biden.

Open borders and the idea that all immigration—whether legal or illegal—is a positive good is a matter of faith for Democrat Party activists. That’s less likely to be true with rank-and-file voters and independents.

“There is no question in my mind that the politics of this is a disaster to Democrats,” said Howard Wolfson, a former deputy and political adviser to former New York Mayor Michael Bloomberg, in an interview with The New York Times.

“This issue alone has the potential to cost Democrats the House, because it is such a huge issue in New York City and the coverage of it is clearly heard and seen by voters in all of these swing districts in the suburbs,” Wolfson said.

He described the issue as a “ticking time bomb” for Democrats.

I’d say the bomb already has gone off.

Since Biden entered the White House in January 2021, a historic stream of illegal immigrants has poured across the U.S. southern border. This has had catastrophic consequences for many swamped communities in Texas and Arizona especially. They’ve shouldered the burden of the border crisis for years, so it’s a little rich for New York to be throwing a pity party.

It obviously would be better if the federal government was doing its job and enforcing our laws, but until that time there’s little border states can do to “fix” the situation. All they can do is mitigate the damage.

The Biden administration has done all it can to make sure that the border remains nice and open, er, “secure.”

The administration’s actions have made it clear that Biden and his top officials want to flood the country with illegal immigrants.

And that’s where border-state busing comes in.

Instead of carrying the entire burden of the Biden-led border disaster, Republican governors such as Greg Abbott in Texas, Ron DeSantis in Florida, and Doug Ducey in Arizona decided to ship illegal immigrants to places such as Chicago, New York, the District of Columbia, and, most amusingly, Martha’s Vineyard.

This is hardly ideal. But if the federal government is going to foist open borders on the country, why not at least force the people who voted for this nonsense to pay more of the price for it?

Of course, Democrats in those destinations pointed fingers at the Republican governors for their newfound troubles, and some left-wing political commentators tried to say that shipping illegal immigrants to Martha’s Vineyard—a posh, liberal vacation destination—was akin to Nazism.

Biden’s trusty allies in the legacy media have done all they can to “contextualize” the immigration issue to protect the president from criticism.

However, much like with the crime surge, it’s hard to pull the wool over the eyes of the American people forever when they literally see the consequences of bad policies in their neighborhoods.

Thanks to Biden, the bill for once low-cost, sanctuary-city virtue signaling has come due.

I suggest that if Democrat politicians want federal aid to care for illegal immigrants, they should demand that the White House work to restore the policies of the previous administration and actually attempt to get control of the border. The excuses have run out, the border crisis has become a national crisis, and blame for this mess falls on the “big guy” in the Oval Office.

Democrats’ demands for more money should be met with a resounding “no” until the actual problem is fixed at its source.

https://www.zerohedge.com/political/busing-illegal-immigrants-blue-america-working

NYPD To Send Drones Over Backyard Barbecues This Weekend

 Want to throw a barbecue in NYC this weekend? The NYPD's got you covered - with drones.

According to AP, the city plans to pilot the unmanned aircraft in response to complains about large gatherings over labor day weekend - including private events.

"If a caller states there’s a large crowd, a large party in a backyard, we’re going to be utilizing our assets to go up and go check on the party," said assistant NYPD Commissioner, Kaz Daughtry.

Privacy advocates, and anyone who's not down with bullshit police surveillance, naturally flipped their lid at the announcement.

"It’s a troubling announcement and it flies in the face of the POST Act," said privacy and technology strategist Daniel Schwarz of the NY Civil Liberties Union, referring to a 2020 city law that requires the NYPD to let people know about their surveillance tactics. "Deploying drones in this way is a sci-fi inspired scenario."

The move was announced during a security briefing focused on J’ouvert, an annual Caribbean festival marking the end of slavery that brings thousands of revelers and a heavy police presence to the streets of Brooklyn. Daughtry said the drones would respond to “non-priority and priority calls” beyond the parade route.

Like many cities, New York is increasingly relying on drones for policing purposes. Data maintained by the city shows the police department has used drones for public safety or emergency purposes 124 times this year, up from just four times in all of 2022. They were spotted in the skies after a parking garage collapse earlier this year and when a giveaway event devolved into teenage mayhem. -AP

Mayor Eric Adams, no surprise, wants the NYPD to embrace the "endless" potential of drones, citing Israel's use of them after visiting last week. 

Privacy advocates say that regulations aren't sufficient to deploy mass drone surveillance, and opens the door to spying that would be illegal if conducted by a human cop.

"One of the biggest concerns with the rush to roll out new forms of aerial surveillance is how few protections we have against seeing these cameras aimed at our backyards or even our bedrooms," said Albert Fox Cahn, the executive director of the Surveillance Technology Oversight Project (STOP).

According to the report, approximately 1,400 police departments nationwide are using drones in some form, according to the ACLU.

https://www.zerohedge.com/technology/nyc-police-send-drones-over-backyard-barbecues-weekend

Immutep: Baird Predicting Significant Growth Potential

 On August 28, 2023, Baird analyst Joel Beatty expressed his confidence in Immutep (NASDAQ:IMMP) by reiterating an “Outperform” rating and maintaining a price target of $7. This forecast indicates a significant growth potential for the stock, considering its current share price of $2.11. Notably, other stock analysts also share a positive outlook on Immutep, with an average 12-month stock price projection of $8.50, suggesting a potential increase of 349.74%. It is crucial to acknowledge that these forecasts and targets are based on the opinions of analysts and prevailing market trends, and the actual performance of the stock may deviate from these predictions.

https://beststocks.com/positive-outlook-for-immutep-nasdaq-immp-with/

Multiple sclerosis drug can be used as Alzheimer's therapy

 A team of researchers at the University of Kentucky has found that a drug used to treat multiple sclerosis (MS) is potentially effective as a therapy for Alzheimer's disease.

Alzheimer's is a progressive and irreversible neurological disorder. It's estimated 6.2 million Americans aged 65 and older are living with the disease that affects cognitive function, memory and behavior.

"We stand at the threshold of a critical endeavor to develop new treatment strategies against Alzheimer's disease," said Erhard Bieberich, Ph.D., a professor in the Department of Physiology in the UK College of Medicine. "We've uncovered that a medication already on the market, ponesimod (brand name 'Ponvory'), can reduce one of the hallmarks of this disease: neuroinflammation."

The findings were published in the journal eBioMedicine, part of The Lancet Discovery Science series in August.

The team studied ponesimod, an oral medication that the U.S. Food and Drug Administration (FDA) has approved to treat relapsing forms of MS. The medication reduces inflammation in the brain by targeting a specific receptor in the immune system to help regulate the body's response and prevent it from attacking the central nervous system. This receptor is activated by a lipid termed sphingosine-1-phosphate, the function of which is studied by the Bieberich lab.

"We are the first to show that ponesimod is effective in a mouse model for Alzheimer's disease," said Bieberich. "Since this drug is already in clinical use for therapy of relapsing multiple sclerosis, it is immediately available to be used in Alzheimer's disease therapy as well."

UK researchers homed in on a specific type of cell found in the central nervous system called microglia. The cells have several functions in our bodies, including regulating inflammatory responses in the central nervous system—the brain and the spinal cord.

Dysfunctional microglia are connected to neurodegenerative diseases like Alzheimer's because those cells help clear out the buildup of abnormal protein deposits in the brain—a distinct characteristic of the disease. Those buildups disrupt the communication between the brain's nerve cells and eventually die off.

"The clearance of those proteins is an important target for Alzheimer's disease therapy," said Zhihui Zhu, Ph.D., first-author of the study and one of the scientists in Bieberich's lab. "In our study, we reprogrammed microglia into neuron-protective cells that clean up toxic proteins in the brain, reduce Alzheimer's neuroinflammatory pathology, and improve memory in the mouse model."

As part of the project, researchers studied mice with specific genetic strains that express the major features of Alzheimer's in their brains. They treated half of the mice with ponesimod and measured specific cell activity in the brain. The mice's spatial memory was also tested through a maze behavior test.

"That specific test is a measure of the spontaneous tendency of the mice to alternate their free choices to enter the two arms of the maze," said Zhu. "Our tests indicate ponesimod rescues attention and working memory in mice with advanced Alzheimer's pathology."

Scientists also worked with UK's Alzheimer's Disease Research Center within the Sanders-Brown Center on Aging to obtain human brain samples to study. The data collected from those tests were consistent and also indicated ponesimod can be used as a therapy for Alzheimer's.

"Neuroinflammation is a hallmark of Alzheimer's, one of the major causes for disease progression and a promising target for therapy," said Bieberich. "Our study shows strong experimental evidence that ponesimod may be a therapeutic drug, which not only reduces neuroinflammation but also enhances the clearance of neurotoxic proteins in the brain in middle and late-stage Alzheimer's."

More information: Zhihui Zhu et al, The S1P receptor 1 antagonist Ponesimod reduces TLR4-induced neuroinflammation and increases Aβ clearance in 5XFAD mice, eBioMedicine (2023). DOI: 10.1016/j.ebiom.2023.104713

https://medicalxpress.com/news/2023-09-multiple-sclerosis-drug-alzheimer-therapy.html

Federal government to regulate staffing at nursing homes for first time

 Nursing homes will soon have to meet federal minimum staffing requirements, the U.S. Department of Health and Human Services (HHS) announced Friday.

"Establishing minimum staffing standards for nursing homes will improve resident safety," HHS Secretary Xavier Becerra said in an agency news release announcing the proposal.

"When facilities are understaffed, residents suffer. They might be unable to use the bathroom, shower, maintain hygiene, change clothes, get out of bed or have someone respond to their call for assistance," Becerra said. "Comprehensive staffing reforms can improve working conditions, leading to higher wages and better retention for this dedicated workforce."

The proposal would set the minimum staffing that is equivalent to 3 hours per resident per day. Just over a half hour of that time would be from a registered nurse. Facilities would be required to have an RN on staff 24 hours a day, every day.

It is "an important first step," said Chiquita Brooks-LaSure, who heads the U.S. Centers for Medicare and Medicaid Services, which oversees nursing homes.

Right now, average U.S. nursing home caregiver staffing is 3.6 hours per resident per day, with an RN working for more than a half hour of that time, according to the Associated Press.

Still, officials said most nursing homes would need to increase staffing.

"I would caution anyone who thinks that the status quo—in which there is no federal floor for nursing home staffing—is preferable to the standards we're proposing," Becerra aide Stacy Sanders told the AP. "This standard would raise staffing levels for more than 75% of nursing homes, bringing more nurse aides to the bedside and ensuring every nursing home has a registered nurse on site 24/7."

The United States has nearly 15,000 nursing homes that care for 1.2 million people.

A 2001 study funded by CMS had recommended a much higher threshold of 4.1 hours of nursing care per resident daily, the AP reported.

The announcement of these new, but lower than first sought, thresholds disappointed advocates, who have said the requirements only consider the point at which someone could experience harm not overall quality of life, the AP reported.

"This was not the time for an incremental step," Richard Mollot, who leads the Long Term Care Community Coalition, told the AP. "You really had a once-in-a-generation opportunity."

On the other side of the issue, the American Health Care Association had lobbied against staffing mandates, citing insufficient Medicaid subsidies, hiring and retention issues and home closures.

AHCA President and CEO Mark Parkinson pointed out that "nursing homes are facing the worst labor shortage in our sector's history, and seniors' access to care is under threat.

"This unfunded mandate, which will cost billions of dollars each year, will worsen this growing crisis. It requires nursing homes to hire tens of thousands of nurses that are simply not there," he said in an association news release.

In all, 38 states and the District of Columbia have their own staffing requirements, some quite low.

Residents and low-paid nurse's aides have long dealt with staffing issues, the AP reported.

Those shortages were exacerbated during the pandemic, when more than 167,000 U.S. nursing home residents died from the virus.

Yet staffing shrunk afterward, with 218,200 fewer employees now than in February 2020, according to the U.S. Bureau of Labor Statistics.

The proposed minimum staffing rule now enters a public comment period.

https://medicalxpress.com/news/2023-09-federal-staffing-nursing-homes.html

LDL not the be all, end all in heart disease, heart attacks and stroke

 Despite advances in treatment for high cholesterol, heart disease remains the leading cause of death in the U.S. Scientists at the Medical College of Wisconsin (MCW) are investigating the role of a form of cholesterol called very-low-density lipoprotein—and their findings may lead to new treatment options in the future.

The research team is led by Ze Zheng, MBBS, Ph.D., MCW assistant professor of medicine (endocrinology and molecular medicine); co-leader of the MCW Cardiovascular Center's Atherosclerosis, Thrombosis and Vascular Biology Program; and associate investigator at Versiti Blood Research Institute. The team's findings were recently published in Science, where Dr. Zheng served as the paper's senior author.

François Poulletier de la Salle successfully isolated cholesterol for the first time from a gallstone in 1769 when his peers believed blood contained only a single protein and no fat. Scientists worked busily to define its molecular formula and shape, and better understand its connection to the accumulation of plaque in blood vessels and the development of heart disease. The first statin was approved by the Food and Drug Administration (FDA) in 1987 to treat patients with high cholesterol and reduce their risk of suffering heart attacks and strokes. In 2015, the FDA approved a new type of drug, known as proprotein convertase subtilisin-kexin type 9 inhibitors, to give cardiologists another tool for patients whose cholesterol levels are still too high after treatment with statins alone.

Yet, heart disease is still the leading cause of death in the U.S. according to the Centers for Disease Control and Prevention and stroke continues to be a major issue as the fifth leading cause of death. One clinical trial following patients taking proprotein convertase subtilisin-kexin type 9 inhibitors demonstrated a benefit, while also revealing an opportunity for improvement as the absolute risk reduction was considered modest at 1.5%.

"It is clear that there is more going on than just what statins and these newer inhibitor drugs can control," says Dr. Zheng. "More therapies are needed, and to get them we need to know more about other sources of risk for heart disease, especially heart attacks and strokes."

Several forms of cholesterol circulate in our bloodstream. The type commonly referred to as "bad cholesterol" is carried by a protein called apolipoprotein B (apoB) which forms well-structured particles with lipids and proteins. These particles serve as stable vehicles for transporting lipids such as cholesterol in the bloodstream. These lipid-rich particles mostly include very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL). The current drugs for lowering cholesterol reduce LDL levels. While substantial evidence shows that LDL is important to control, it is not the only risk factor for heart disease. In fact, the other lipoproteins in the same group as LDL are not reduced by much with available treatments. Dr. Zheng and team are investigating how to reduce levels of other members of this family of lipoproteins, especially VLDL.

"With my background in lipid metabolism, I found myself consistently checking lipid levels even during studies regarding blood clot lysis and how an impairment in the body's ability to remove blood clots affects the risk of blood vessel blockages," Dr. Zheng adds. "I was just naturally curious about it, and I noticed that a protein I was studying may have an effect on the amount of circulating cholesterol."

In prior research, Dr. Zheng has helped define a new cellular source of this protein, tissue-type plasminogen activator (tPA), and its role in breaking down blood clots and preventing blood vessel blockages. To understand its potential influence on cholesterol levels, her team used a gene-editing technique to stop liver cells from producing tPA in mice prone to blood vessel plaque formation. The scientists found that the mice developed increased lipoprotein-cholesterol in this experiment, and then validated the findings in follow-up studies using human liver cells and a type of rat liver cell known to produce VLDL in a way similar to human liver cells. With these and other experimental results published in Science in September 2023, Dr. Zheng and her team have demonstrated a new, important role that liver tPA influences blood cholesterol levels while underscoring a meaningful connection between the liver, heart, and blood vessels.

"After defining this new role for tPA, we turned our attention to the question of how it changes blood cholesterol levels," notes Wen Dai, MD, research scientist at the Versiti Blood Research Institute.

The liver contributes to the majority of the "bad" apoB-lipoproteins by making VLDL. The team focused on whether and how tPA impacts the process of VLDL assembly in the liver. Microsomal triglyceride transfer protein (MTP) is required for the assembly of VLDL due to its role carrying lipids to the apoB. The scientists determined that tPA binds with the apoB protein in the same place as MTP. The more tPA is present, the fewer opportunities MTP has to connect with apoB and catalyze the creation of new VLDL. If MTP is the quarterback trying to pass a cholesterol football to an open apoB receiver, then tPA is the cornerback breaking up the play.

"Based on our prior research, we knew it also was critical to look at tPA's primary inhibitor," Dr. Zheng says.

Plasminogen activator inhibitor-1 (PAI-1) is known to block the activity of tPA. Scientists also have found a correlation between PAI-1 levels in blood and the development of disease due to plaque formation and blockages in blood vessels. The team found that higher levels of PAI-1 reduced the ability of tPA to bind with apoB proteins, rendering tPA less effective at competing with MTP to prevent VLDL production. Returning to the biological gridiron, PAI-1 might be a decoy receiver that distracts tPA until MTP connects with apoB for a big gain. The team studied this interaction in human subjects with a naturally occurring mutation in the gene carrying the code for PAI-1. The researchers found that these individuals, as predicted, had higher tPA levels and lower LDL and VLDL levels than individuals from the same community who did not have the same mutation.

"We are investigating therapeutic strategies based on these findings regarding tPA, MTP and PAI-1," Dr. Zheng notes. "I think we may be able to reduce the residual cardiovascular risk that has persisted even as treatment has advanced."

More information: Wen Dai et al, Intracellular tPA–PAI-1 interaction determines VLDL assembly in hepatocytes, Science (2023). DOI: 10.1126/science.adh5207

https://medicalxpress.com/news/2023-09-ldl-heart-disease.html