Notably, ACE2 expression is usually a dominant mechanism for unfavorable regulation of RAS conversion of Ang II into the beneficial peptide Ang 1C7, and this significant biochemical and physiological property is being harnessed as a potential therapy for patients with heart failure (39). Rabbit Polyclonal to GSK3beta COVID-19. Angiotensin (Ang)-converting enzyme 2 (ACE2) is usually a membrane-bound aminopeptidase that plays pivotal functions in both heart failure and pulmonary failure (21C23). Previous studies exhibited that SARS-CoV contamination in mouse lungs causes ACE2-dependent myocardial contamination (22, 23). Recent research found that SARS-CoV-2 has a 10- to 20-fold greater binding affinity to ACE2 compared with SARS-CoV, which may explain how SARS-CoV-2 is so easily spread from person-to-person (20). Accordingly, extra attention should be paid to applying strategies for cardiovascular protection during treatment of COVID-19. Interestingly, the protective role of the ACE2/Ang-(1C9) axis is related to cardiovascular remodeling. Under normal physiological conditions, the activity levels of the positive ACE/Ang II axis and unfavorable ACE2/Ang-(1C7) axis of the renin-Ang system (RAS) are in a dynamic equilibrium, which maintains the normal function of the cardiovascular system, including dilating blood vessels, lowering blood pressure, and inhibiting apoptosis (3). Overexpression of ACE2 enhances plaque stability in a rabbit model of atherosclerosis (24). Furthermore, ACE2 overexpression and Ang (17) significantly improve ventricular remodeling and function in a rat model of myocardial infarction (25, 26). Similarly, clinical studies have exhibited that plasma Ang-(1C7) levels in patients with acute myocardial infarction are significantly correlated with myocardial survival index, myocardial infarction area and left ventricular ejection fraction after coronary intervention (27). Previous findings support a significant effect of overexpression of ACE2 and plasma Ang-(1C7) for reducing the incidence and severity of abdominal aortic aneurysm major (28). Notably, this pathway is usually grossly perturbed by SARS-CoV-2 contamination (29, 30), which may result in a decline in ACE2 levels and elevation of plasma Ang-(1C7) levels. The excessive inflammation induced by increased pro-inflammatory factor expression levels may result in a cytokine storm, which contributes to myocardium damage (29, 30). However, ACE2 up-regulation and highly regulated tissue injury are found Thiazovivin in patients with pre-existing cardiomyopathy and other underlying diseases of myocardial injury (31, 32), which may facilitate the invasion of SARS-CoV-2 into the body. Thiazovivin Therefore, patients with cardiomyopathy are more likely to be experience severe COVID-19. experiments and studies in animal models revealed that this mechanism by which SARS-CoV activates the RAS positive axis is usually downregulation of ACE2 levels, which in turn triggers acute severe lung injury (21, 33). Also noteworthy is usually that ACE2 is usually highly expressed in the heart and lungs, but SARS-nCoV-2 mainly affects the alveolar epithelium with only a minimal effect on the heart (34). ACE inhibitor (ACEI) and Ang II receptor antagonist (ARB) can increase the expression of ACE2 or prevent the loss of ACE2, effects that contribute to the mechanisms of ACEI/ARB activity. Accordingly, it could be reasonably hypothesized that ACEIs/ARBs might increase the risk of SARS-CoV-2 contamination or induce increased expression of ACE2 in the cardiovascular system and lung tissue, which would aggravate the condition. However, this phenomenon has not been observed clinically (35). One explanation may Thiazovivin be that SARS-CoV-2 rarely invades the blood circulation, limiting viremia. Therefore, the computer virus may not cause myocardial damage directly through the ACE2 pathway. Other explanations may be that this so-called ACE2 proteins of the heart and lungs are slightly different subtypes or that SARS-CoV-2 does not function through ACE2 at all. Importantly, biological experiments have shown that this severe phenotype of mice with a single mutation of Ace2 can be rescued by ACE deficiency resulting from further deletion of Thiazovivin the Ace gene17, indicating that the balance of ACE2/ACE levels is the vital target for preventing lung injury and achieving lung Thiazovivin protection (23). Therapeutic Strategies for Heart Failure in COVID-19 Patients SARS-CoV-2 invades the human body in the same way as SARS-CoV by binding to Spike protein, which causes down-regulation of tissue ACE2 expression and elevation of AngII expression (20, 36, 37). Given that both the heart and lung.