Objectives In March 2020, the World Health Organization declared that an infectious respiratory disease caused by a new severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2, causing coronavirus disease 2019 (COVID-19)] became a pandemic. In our study, we have analyzed a large publicly available dataset, the Genome Aggregation Database (gnomAD), as well as a cohort of 37 Russian patients with COVID-19 to assess the influence of different classes of genetic variants in the angiotensin-converting enzyme-2 ( ACE2 ) gene on the susceptibility to COVID-19 and the severity of disease outcome. Results We demonstrate that the European populations slightly differ in alternative allele frequencies at the 2,754 variant sites in ACE2 identified in the gnomAD database. We find that the Southern European population has a lower frequency of missense variants and slightly higher frequency of regulatory variants. However, we found no statistical support for the significance of these differences. We also show that the Russian population is similar to other European populations when comparing the frequencies of the ACE2 variants. Evaluation of the effect of various classes of ACE2 variants on COVID-19 outcome in a cohort of Russian patients showed that common missense and regulatory variants do not explain the differences in disease severity. At the same time, we find several rare ACE2 variants (including rs146598386, rs73195521, rs755766792, and others) that are likely to affect the outcome of COVID-19. Our results demonstrate that the spectrum of genetic variants in ACE2 may partially explain the differences in severity of the COVID-19 outcome.
Inflammation, cardiac remodeling, and fibrosis are potentially important pathways in the pathogenesis of cardiovascular diseases. Complications of atherosclerosis are one of the leading causes of death in the world. Effective prevention of cardiovascular disease by adequate control of major cardiovascular risk factors can provide substantial public health gains. However, detection and control of major cardiovascular risk factors continues to be a major challenge because of poor awareness of an individual's status. A solution to this problem is important for an early identification and appropriate correction of cardiovascular risk factors. Atherosclerotic plaque development is regarded as a chronic inflammatory process which involves interactions between lipids, immune cells and the artery wall. Numerous evidence suggests that inflammation plays an important role in all stages of the atherosclerotic process. The study of associations of inflammatory biomarkers has led to the idea that the panel of inflammatory biomarkers can identify people at high risk of developing atherosclerosis and cardiovascular diseases when anti-inflammatory treatment can prevent further unfavorable events. The most common forms of cardiovascular diseases are caused by atherosclerosis, the progressive thinning of blood vessels due to accumulation of lipids within the arterial wall. While many factors are known to influence the development and progression of atherosclerosis, circulating levels of cholesterol and lipoprotein complexes are the most important risk factors and mediators of atherosclerotic disease. Key regulators of lipid metabolism and/or the development of atherosclerosis have diagnostic, prognostic and therapeutic potential for cardiovascular diseases.
The strategy of heart tissue engineering is simple enough: first remove all the cells from a organ then take the protein scaffold left behind and repopulate it with stem cells immunologically matched to the patient in need. While various successful methods for decellularization have been developed, and the feasibility of using decellularized whole hearts and extracellular matrix to support cells has been demonstrated, the reality of creating whole hearts for transplantation and of clinical application of decellularized extracellular matrix-based scaffolds will require much more research. For example, further investigations into how lineage-restricted progenitors repopulate the decellularized heart and differentiate in a site-specific manner into different populations of the native heart would be essential. The scaffold heart does not have to be human. Pig hearts carries all the essential components of the extracellular matrix. Through trial and error, scaling up the concentration, timing and pressure of the detergents, researchers have refined the decellularization process on hundreds of hearts and other organs, but this is only the first step. Further, the framework must be populated with human cells. Most researchers in the field use a mixture of two or more cell types, such as endothelial precursor cells to line blood vessels and muscle progenitors to seed the walls of the chambers. The final challenge is one of the hardest: vascularization, placing a engineered heart into a living animal, integration with the recipient tissue, and keeping it beating for a long time. Much remains to be done before a bioartificial heart is available for transplantation in humans.
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