Gene expression levels of the enzyme, OLAH, is critical in determining disease severity

Good news! Amazing stuff!

"... Scientists have identified a gene associated with whether patients hospitalised with respiratory viral infections experience mild disease or life-threatening complications.

According to the new study published in Cell, expression levels of the gene, OLAH, is critical in determining disease severity. ..."

From the highlights and abstract:

"Highlights

• Fatal H7N9 flu patients express high OLAH levels throughout hospitalization

• High OLAH levels are detected in severe H1N1, COVID-19, RSV, and MIS-C patients

• Olah−/− mice are protected from lethal influenza disease and excessive inflammation

• Olah expression in macrophages drives viral infection and an inflammatory milieu

Summary

Respiratory infections cause significant morbidity and mortality, yet it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning fatal disease. Transcriptomics strongly linked oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating fatty acid production, with fatal A(H7N9) early after hospital admission, persisting until death. Recovered patients had low OLAH expression throughout hospitalization. High OLAH levels were also detected in patients hospitalized with life-threatening seasonal influenza, COVID-19, respiratory syncytial virus (RSV), and multisystem inflammatory syndrome in children (MIS-C) but not during mild disease. In olah−/− mice, lethal influenza infection led to survival and mild disease as well as reduced lung viral loads, tissue damage, infection-driven pulmonary cell infiltration, and inflammation. This was underpinned by differential lipid droplet dynamics as well as reduced viral replication and virus-induced inflammation in macrophages. Supplementation of oleic acid, the main product of OLAH, increased influenza replication in macrophages and their inflammatory potential. Our findings define how the expression of OLAH drives life-threatening viral disease."

Gene linked to life-threatening respiratory viral infections

High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases

Graphical abstract

Study gives hint on South Asians’ higher risk of cardiovascular disease

Good news!

"South Asian people have lower levels of stem cells key to regenerating blood vessels, according to a new study that sheds light on a potential reason for the population’s increased risk of heart disease (double the risk of people of European descent). ..."

From the abstract:

"Background

South Asian individuals shoulder a disproportionate burden of cardiometabolic diseases.

Objectives

The purpose of this study was to determine if vascular regenerative cell content varies significantly between South Asian and White European people.

Methods

Between January 2022 and January 2023, 60 South Asian and 60 White European adults with either documented cardiovascular disease or established diabetes with ≥1 other cardiovascular risk factor were prospectively enrolled. Vascular regenerative cell content in venous blood was enumerated using a flow cytometry assay that is based on high aldehyde dehydrogenase (ALDHhi) activity and cell surface marker phenotyping. The primary outcome was the difference in frequency of circulating ALDHhi progenitor cells, monocytes, and granulocytes between the 2 groups.

Results

Compared with White European participants, those of South Asian ethnicity were younger (69 ± 10 years vs 66 ± 9 years; P < 0.05), had lower weight (88 ± 19 kg vs 75 ± 13 kg; P < 0.001), and exhibited a greater prevalence of type 2 diabetes (62% vs 92%). South Asian individuals had markedly lower circulating frequencies of pro-angiogenic ALDHhiSSClowCD133+ progenitor cells (P < 0.001) and ALDHhiSSCmidCD14+CD163+ monocytes with vessel-reparative capacity (P < 0.001), as well as proportionally more ALDHhi progenitor cells with high reactive oxygen species content (P < 0.05). After correction for sex, age, body mass index, and glycated hemoglobin, South Asian ethnicity was independently associated with lower ALDHhiSSClowCD133+ cell count.

Conclusions

South Asian people with cardiometabolic disease had less vascular regenerative and reparative cells suggesting compromised vessel repair capabilities that may contribute to the excess vascular risk in this population. (The Role of South Asian vs European Origins on Circulating Regenerative Cell Exhaustion [ORIGINS-RCE]; NCT05253521)"

Johns Hopkins Bloomberg School of Public Health: Global Health NOW

Vascular Regenerative Cell Deficiencies in South Asian Adults (no public access)

Central illustration (aka graphical abstract?)

Common dietary nutrient manganese blasts blood vessel plaques in study

Good news!

"... [researchers] figured out that the element [manganese] can bind to a complex needed by lipoproteins, chemical carriers that move lipids including cholesterol and triglycerides, into the bloodstream. This complex known as the coat protein complex II (COPII) needs to maintain a very precise chemical balance that the manganese disrupts. As a result of this disruption, the researchers found that in the mice they studied, even oral manganese dramatically reduced blood concentration of lipids and removed plaques that had been established in the rodents' blood vessels. ..."

From what is believed to be the abstract:

"Precise control of circulating lipid levels is vital in both health and disease. We recently uncovered that bulk lipids, transported by lipoproteins, enter the circulation initially via the coat protein complex II (COPII) in a condensation-dependent manner. Divalent manganese, acting as a signaling messenger, selectively controls COPII condensation to regulate lipid homeostasis in vivo. Here we present evidence for a manganese-based therapy in murine models of hypolipidemia and hyperlipidemia, aided by advanced in vivo multimodal imaging of atherosclerosis. Dietary titration of manganese supply enables tailored control of circulating lipid levels in whole animals, with no apparent toxicity. Strikingly, elevating the manganese signal through diets could not only effectively treat pathological hyperlipidemia, but further achieve significant reversal of atherosclerotic plaques. Hence, the study provides critical proof-of-principle for a novel therapy for deadly cardiovascular diseases with a potentially broad impact"

Common dietary nutrient blasts blood vessel plaques in study

Manganese therapy for dyslipidemia and plaque reversal in murine models (open access)

Treating a Heart Attack before It Happens

Good news! As they say one ounce of prevention is better than one pound of cure!

Did these scientists find a "cardiac fountain of youth"?

"... researchers ... have now activated a cellular mechanism in healthy mouse hearts that makes these mice resilient to future heart attacks – even when they occur months later. ...
A mouse whose ERBB2 had been activated when it was three months old recovered from cardiac injury that happened five months later. ...
The study ... focused on genetically engineered mice whose cardiomyocytes – the cells that make up the heart muscle tissue – overexpress a gene that triggers cell division in mice and other mammals, including humans. In previous studies ... had found that the gene, ERBB2, causes cell division in cardiomyocytes – a remarkable occurrence because at around the time of birth these cells lose their capacity to multiply. ...

When, in previous studies, ... team had managed to trigger the division of cardiomyocytes – by switching on ERBB2 briefly in these cells – overall heart function actually decreased temporarily, rather than improving straightaway. This happened because the ERBB2-expressing cardiomyocytes underwent dedifferentiation, meaning that they reverted to a less specialized state, closer to that of a fetal heart. This, in turn, limited their ability to contract, which is needed for proper heart function. But once the overexpression had stopped, the cardiomyocytes underwent redifferentiation – that is, they became highly specialized again – and cardiac performance improved.

In the new study, ... notice some significant differences in gene expression between the two populations. ... “We had assumed that everything returns to normal after ERBB2 is switched off in the cardiomyocytes. Yet here we were, seeing a different genetic pattern – overexpression in some genes and underexpression in others – following ERBB2 activation. In other words, we found long-term effects. ...
To test this hypothesis, the researchers reversed the order of their previous experiments with ERBB2. Instead of switching ERBB2 on in injured mice to make their cardiomyocytes divide, they first switched it on in healthy mice for a few weeks and then switched it off again. Next, the researchers observed how the hearts of those mice coped with an injury. The result: Mice that had been made to overexpress ERBB2 recovered, but others did not. “The data made our jaws drop,” ... “We had found a cardiac fountain of youth in those mice, a novel way of making the heart younger and stronger.””

This discovery made ... wonder whether ERBB2 expression could be calibrated for improved cardiac performance. “It made us think that ERBB2 wasn’t just a switch that prevents differentiation, but part of a mechanism that could make the heart younger and more resilient,” ..."

From the abstract:

"Cardiomyocyte proliferation and dedifferentiation have fueled the field of regenerative cardiology in recent years, whereas the reverse process of redifferentiation remains largely unexplored. Redifferentiation is characterized by the restoration of function lost during dedifferentiation. Previously, we showed that ERBB2-mediated heart regeneration has these two distinct phases: transient dedifferentiation and redifferentiation. Here we survey the temporal transcriptomic and proteomic landscape of dedifferentiation–redifferentiation in adult mouse hearts and reveal that well-characterized dedifferentiation features largely return to normal, although elements of residual dedifferentiation remain, even after the contractile function is restored. These hearts appear rejuvenated and show robust resistance to ischemic injury, even 5 months after redifferentiation initiation. Cardiomyocyte redifferentiation is driven by negative feedback signaling and requires LATS1/2 Hippo pathway activity. Our data reveal the importance of cardiomyocyte redifferentiation in functional restoration during regeneration but also protection against future insult, in what could lead to a potential prophylactic treatment against ischemic heart disease for at-risk patients."

Treating a Heart Attack before It Happens - Life Sciences | Weizmann Wonder Wander - News, Features and Discoveries A preventive procedure, performed on healthy mice, improved their recovery from later-occurring cardiac injury, reshaping our knowledge of regeneration in hearts – and possibly other organs

Redifferentiated cardiomyocytes retain residual dedifferentiation signatures and are protected against ischemic injury (no public access)

Mouse hearts after injury. Scar tissue (red) represents the extent of damage to the heart muscle. The damage was significantly reduced in mice whose ERBB2 gene had been temporarily activated (bottom row), compared to the controls (upper row)

Cardiovascular Risk Factor and obesity have increased in US Adults Aged 20 to 44 Years, from 2009 to 2020

Not good news!

How much are social media, video games and the like to blame? Our recreational behavior has changed significantly over the past several decades.

How about e-bikes? When I see teenagers on e-bikes these days, they do not use the pedals anymore like our generation used to do, they just sit on the bike and enjoy the fast ride. A sign of the times!

What is the ludicrous and desperate spin of the leftist JHU Bloomberg School of Public Health:

"Disparities [???]: Racial inequities [???] in the US contribute to problems like food insecurity [???] —which in turn drive worsening outcomes:"

Michael Bloomberg do you know or are you aware of what is being done in your name and with your money? Doubtful!

Have you ever wondered where the expression spin doctor comes from? 😊

"... Findings  In this serial cross-sectional study of 12 924 adults aged 20 to 44 years, there were increases in the prevalence of diabetes (from 3.0% to 4.1%) and obesity (from 32.7% to 40.9%), no improvement in the prevalence of hypertension (from 9.3% to 11.5%), and a decrease in the prevalence of hyperlipidemia (from 40.5% to 36.1%) from 2009-2010 to 2017-2020. Black young adults had the highest rates of hypertension over the study period, and increases in hypertension were observed among Mexican American and other Hispanic adults, while Mexican American adults experienced a significant rise in diabetes. Blood pressure control did not significantly change among young adults treated for hypertension, while glycemic control remained suboptimal throughout the study period. ..."

From the abstract:

"Abstract

Importance  Declines in cardiovascular mortality have stagnated in the US over the past decade, in part related to worsening risk factor control in older adults. Little is known about how the prevalence, treatment, and control of cardiovascular risk factors have changed among young adults aged 20 to 44 years.

Objective  To determine if the prevalence of cardiovascular risk factors (hypertension, diabetes, hyperlipidemia, obesity, and tobacco use), treatment rates, and control changed among adults aged 20 to 44 years from 2009 through March 2020, overall and by sex and race and ethnicity.

Design, Setting, and Participants  Serial cross-sectional analysis of adults aged 20 to 44 years in the US participating in the National Health and Nutrition Examination Survey (2009-2010 to 2017–March 2020).

Main Outcomes and Measures  National trends in the prevalence of hypertension, diabetes, hyperlipidemia, obesity, and smoking history; treatment rates for hypertension and diabetes; and blood pressure and glycemic control in those receiving treatment.

Results  Among 12 924 US adults aged 20 to 44 years (mean age, 31.8 years; 50.6% women), the prevalence of hypertension was 9.3% (95% CI, 8.1%-10.5%) in 2009-2010 and 11.5% (95% CI, 9.6%-13.4%) in 2017-2020. The prevalence of diabetes (from 3.0% [95% CI, 2.2%-3.7%] to 4.1% [95% CI, 3.5%-4.7%]) and obesity (from 32.7% [95% CI, 30.1%-35.3%] to 40.9% [95% CI, 37.5%-44.3%]) increased from 2009-2010 to 2017-2020, while the prevalence of hyperlipidemia decreased (from 40.5% [95% CI, 38.6%-42.3%] to 36.1% [95% CI, 33.5%-38.7%]). Black adults had high rates of hypertension across the study period (2009-2010: 16.2% [95% CI, 14.0%-18.4%]; 2017-2020: 20.1% [95% CI, 16.8%-23.3%]), and significant increases in hypertension were observed among Mexican American adults (from 6.5% [95% CI, 5.0%-8.0%] to 9.5% [95% CI, 7.3%-11.7%]) and other Hispanic adults (from 4.4% [95% CI, 2.1%-6.8%] to 10.5% [95% CI, 6.8%-14.3%]), while Mexican American adults had a significant rise in diabetes (from 4.3% [95% CI, 2.3%-6.2%] to 7.5% [95% CI, 5.4%-9.6%]). The percentage of young adults treated for hypertension who achieved blood pressure control did not significantly change (from 65.0% [95% CI, 55.8%-74.2%] in 2009-2010 to 74.8% [95% CI, 67.5%-82.1%] in 2017-2020], while glycemic control among young adults receiving treatment for diabetes remained suboptimal throughout the study period (2009-2010: 45.5% [95% CI, 27.7%-63.3%]) to 2017-2020: 56.6% [95% CI, 39.2%-73.9%]).

Conclusions and Relevance  In the US, diabetes and obesity increased among young adults from 2009 to March 2020, while hypertension did not change and hyperlipidemia declined. There was variation in trends by race and ethnicity."

"... The national increases in diabetes and obesity among young adults in the US have major public health implications. The rise in obesity—to more than 40% in young adults18,19—corresponds with increases in sedentary behaviors over the same period and likely contributed to other cardiometabolic trends observed in our study. ..."

Cardiovascular Risk Factor Prevalence, Treatment, and Control in US Adults Aged 20 to 44 Years, 2009 to March 2020 | Adolescent Medicine | JAMA | JAMA Network (open access)

Groundbreaking research uncovers what protects us from heart disease

Good news!

"... the research found that endothelial progenitor cells – which help repair the inner lining of a blood vessel following vascular injury – as well as telomere length, may play a critical role in preventing heart disease. The results of the study were recently published in the Coronary Artery Disease medical journal. ...

the research set out to uncover why some people never develop heart disease despite having high-risk profiles (diabetes, smoking, excess cholesterol, etc.), while others do. ...
Researchers found that patients with a high risk for coronary artery disease but with healthy arteries had greater endothelial progenitor cell function than patients with existing heart disease. In addition, they also discovered that these cells had longer telomeres (which indicate a cell’s lifespan) in individuals with normal arteries. Telomere length has previously been shown to be correlated with overall cell health. ..."

From the abstract:

"Background 

Endothelial progenitor cells (EPCs) have an important role in repair following vascular injury. Telomere length has been shown to be correlated with genome stability and overall cell health. We hypothesized that both EPCs and telomere size are related to protective mechanisms against coronary artery disease. Our aim was to evaluate the level and function of circulating EPCs and telomere length in patients with multiple cardiovascular risk factors and anatomically normal coronary arteries vs. matched controls.

Methods 

We included 24 patients, with coronary CTA demonstrating normal coronaries and a high risk of CAD of >10% by ASCVD risk estimator. Control groups included 17 patients with similar cardiovascular profiles but with established CAD and a group of 20 healthy volunteers. ...

Results 

Patients with high risk for CVD and normal coronaries had augmented EPCs function, compared with the CAD group (1.1 vs. 0.22 CFU/f; P = 0.04) and longer telomeres compared with the CAD group (10.7 kb vs. 2.8 kb P = 0.015). These patients displayed a similar profile to the healthy group.

Conclusion 

Patients with a high risk for CAD, but normal coronary arteries have EPCs function and telomere length which resemble healthy volunteers, and augmented compared with patients with established CAD, which could serve as a protective mechanism against atherosclerosis development in these high-risk patients."

Groundbreaking research uncovers what protects us from heart disease - The Jerusalem Post Assuta Ashdod-led study finds protective biological factors that prevent the development of atherosclerosis in high-risk individuals.

Identification of protective biologic factors in patients with high cardiovascular risk, but normal coronary arteries (NormCorn) (no public access)

Assuta Ashdod's Dr. Einat Shaked, who led the research with her hands deep in her pants pockets 😊