Icahn School of Medicine Study Shows That The Protein Hypoxia-Inducible Factor 1 Alpha (HIF1α) Plays A Cardioprotective Role In COVID-19 Patients
Source: Aug 11, 2021 3 years, 4 months, 1 week, 5 days, 13 hours, 28 minutes ago
A new study by researchers from the Icahn School of Medicine at Mount Sinai and the Mount Sinai Hospital-New York has found that the protein hypoxia-inducible factor 1 alpha (HIF1α), plays a critical cardioprotective role in COVID-19 patients.
The study findings establishes a direct link of cardiac cellular responses to hypoxic stress with matching functional and histological data, serving as one of the first research findings to bridge previous stand-alone clinical data and cellular data. The protective role of HIF1α in hearts may help predict cardiac involvement in not only COVID-19 patients, but also decipher the underlying mechanisms in other forms of viral cardiomyopathy.
The study findings were published on a preprint server and are currently being peer reviewed.
https://www.medrxiv.org/content/10.1101/2021.08.05.21258160v1
The current COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first emerged in Wuhan, China, in late December 2019, has quickly become the most urgent issue facing scientists worldwide.
It has been reported that the respiratory infection causes cardiac dysfunction in 25-55% patients, including hospitalized patients and non-critical patients.
https://pubmed.ncbi.nlm.nih.gov/32556199/
https://stm.sciencemag.org/content/13/590/eabf7872
Corresponding author, Dr Hina W. Chaudhry from the department of Cardiovascular Regenerative Medicine at Icahn School of Medicine told Thailand Medical News, “Surprisingly, increasing incidents of myocardial injury with sustained cardiac involvement was found in many patients months after recovery from COVID-19, with a proportion of patients with no known history of previous cardiac symptoms.”
The SARS-CoV-2 coronavirus is responsible for triggering respiratory illness leading to symptoms such as difficulty in breathing and chronic pulmonary and cardiovascular hypoxia.
Studies have shown that under low oxygen conditions associated with COVID-19, the
hypoxia-inducible factor 1 alpha (HIF1α), known to be the master regulator of hypoxia, gets stabilized and protects against SARS-CoV-2 infection.
Dr Chaudhry further added, “This study establishes a direct link of cardiac cellular responses to hypoxic stress with matching functional and histological data, serving as one of the first studies to bridge previous stand-alone clinical data and cellular data.”
As previously said above, under low oxygen conditions, HIF1α does not undergo oxygen-dependent proteolysis and accumulates in the nucleus. This accumulation results in dimerization with HIF1β, which then binds to the hypoxia-response elements (HREs).
Dr Chaudhry explained, “HIF1α stabilization leads to an avalanche of transcriptional activities involving angiogenesis, proliferation, homeostasis, inflammation, and metabolic switch.”
Importantly a recent study has shown that st
abilization of HIF1α leads to a decrease in ACE2 receptors, which are the entry point of the SARS-CoV-2 virus.
Another study also suggested that a decrease in SARS-CoV-2 pathogenicity at high altitudes was also due to a decrease in ACE2 receptors in response to hypoxic environments.
The current research involved two groups of COVID-19 patients, those with preserved cardiac function having Ejection Fraction (EF) greater than 50 percent and those with moderate to severe cardiac dysfunction having EF less than 45 percent.
For the study, the echocardiography data, which involved both systolic and diastolic function, was examined along with post-mortem samples.
In addition, the heart samples were immunostained with primary and secondary antibodies.
The detailed study of apoptosis was carried out by the hep of TUNEL assay, which used in situ cell death detection kit.
Quantitative RT-PCR was carried out of the post-mortem lungs to detect the presence of RNA. Finally, Transmission Electron Microscopy (TEM) was performed on a control heart sample that did not have COVID-19 history.
The study team found that in preserved hearts, the expression of HIF1α is mostly in non-myocytes that help protect endothelial cells.
Dr Chaudhry said, “Endothelial cells adapt to hypoxia by activating HIF1α and orchestrating a number of genes involving cellular metabolism, anti-apoptosis, and proinflammatory response.”
It should be noted that the nuclear envelope in low EF heart is thinner than preserved EF heart which results in loss of function, sarcomeric damage, and myofibril abnormalities.
Dr Chaudhry added, “These data suggest that cell-type dependent HIF1α expression is increased in hearts of COVID-19 patients with preserved cardiac function. Our study findings provide compelling evidence of the protective role played by HIF1α in hearts of patients affected by COVID-19.”
She added, “The protective role of HIF1α in hearts may not only help to predict cardiac involvement in COVID-19 patients but also help to understand mechanisms involved in other forms of viral cardiomyopathy.”
Thailand Medical News would like to add that it was found that the phytochemical Tanshinone from Red Sage was able to upregulate HIF1α expression besides also having lung and heart protective functions.
https://www.sciencedirect.com/science/article/pii/S0254627217300547
Red Sage is also an important constituent in our Therapeutic Teas.
https://www.thailandmedical.news/news/new-therapeutic-teas-
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