The potential effects of DPP-4 inhibitors on cardiovascular system in COVID-19 patients.

With the outbreak of a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the public healthcare systems are facing great challenges. Coronavirus disease 2019 (COVID-19) could develop into severe pneumonia, acute respiratory distress syndrome and multi-organ failure. Remarkably, in addition to the respiratory symptoms, some COVID-19 patients also suffer from cardiovascular injuries. Dipeptidyl peptidase-4 (DPP-4) is a ubiquitous glycoprotein which could act both as a cell membrane-bound protein and a soluble enzymatic protein after cleavage and release into the circulation. Despite angiotensin-converting enzyme 2 (ACE2), the recently recognized receptor of SARS-CoV and SARS-CoV-2, which facilitated their entries into the host, DPP-4 has been identified as the receptor of middle east respiratory syndrome coronavirus (MERS-CoV). In the current review, we discussed the potential roles of DPP-4 in COVID-19 and the possible effects of DPP-4 inhibitors on cardiovascular system in patients with COVID-19.

COVID-19 and Cardiovascular Disease.

Coronavirus disease 2019 (COVID-19) is a global pandemic affecting 185 countries and >3 000 000 patients worldwide as of April 28, 2020. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2, which invades cells through the angiotensin-converting enzyme 2 receptor. Among patients with COVID-19, there is a high prevalence of cardiovascular disease, and >7% of patients experience myocardial injury from the infection (22% of critically ill patients). Although angiotensin-converting enzyme 2 serves as the portal for infection, the role of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers requires further investigation. COVID-19 poses a challenge for heart transplantation, affecting donor selection, immunosuppression, and posttransplant management. There are a number of promising therapies under active investigation to treat and prevent COVID-19.

Cardiovascular disease and COVID-19: a consensus paper from the ESC Working Group on Coronary Pathophysiology & Microcirculation, ESC Working Group on Thrombosis and the Association for Acute CardioVascular Care (ACVC), in collaboration with the European Heart Rhythm Association (EHRA).

The cardiovascular system is significantly affected in coronavirus disease-19 (COVID-19). Microvascular injury, endothelial dysfunction, and thrombosis resulting from viral infection or indirectly related to the intense systemic inflammatory and immune responses are characteristic features of severe COVID-19. Pre-existing cardiovascular disease and viral load are linked to myocardial injury and worse outcomes. The vascular response to cytokine production and the interaction between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and angiotensin-converting enzyme 2 receptor may lead to a significant reduction in cardiac contractility and subsequent myocardial dysfunction. In addition, a considerable proportion of patients who have been infected with SARS-CoV-2 do not fully recover and continue to experience a large number of symptoms and post-acute complications in the absence of a detectable viral infection. This conditions often referred to as 'post-acute COVID-19' may have multiple causes. Viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition. Systemic inflammatory response to COVID-19 has the potential to increase myocardial fibrosis which in turn may impair cardiac remodelling. Here, we summarize the current knowledge of cardiovascular injury and post-acute sequelae of COVID-19. As the pandemic continues and new variants emerge, we can advance our knowledge of the underlying mechanisms only by integrating our understanding of the pathophysiology with the corresponding clinical findings. Identification of new biomarkers of cardiovascular complications, and development of effective treatments for COVID-19 infection are of crucial importance.

Protein kinase CK2: a potential therapeutic target for diverse human diseases.

CK2 is a constitutively active Ser/Thr protein kinase, which phosphorylates hundreds of substrates, controls several signaling pathways, and is implicated in a plethora of human diseases. Its best documented role is in cancer, where it regulates practically all malignant hallmarks. Other well-known functions of CK2 are in human infections; in particular, several viruses exploit host cell CK2 for their life cycle. Very recently, also SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been found to enhance CK2 activity and to induce the phosphorylation of several CK2 substrates (either viral and host proteins). CK2 is also considered an emerging target for neurological diseases, inflammation and autoimmune disorders, diverse ophthalmic pathologies, diabetes, and obesity. In addition, CK2 activity has been associated with cardiovascular diseases, as cardiac ischemia-reperfusion injury, atherosclerosis, and cardiac hypertrophy. The hypothesis of considering CK2 inhibition for cystic fibrosis therapies has been also entertained for many years. Moreover, psychiatric disorders and syndromes due to CK2 mutations have been recently identified. On these bases, CK2 is emerging as an increasingly attractive target in various fields of human medicine, with the advantage that several very specific and effective inhibitors are already available. Here, we review the literature on CK2 implication in different human pathologies and evaluate its potential as a pharmacological target in the light of the most recent findings.

Dual role for angiotensin-converting enzyme 2 in Severe Acute Respiratory Syndrome Coronavirus 2 infection and cardiac fat.

Angiotensin-converting enzyme 2 (ACE2) has been an increasingly prevalent target for investigation since its discovery 20 years ago. The finding that it serves a counterregulatory function within the traditional renin-angiotensin system, implicating it in cardiometabolic health, has increased its clinical relevance. Focus on ACE2's role in cardiometabolic health has largely centered on its apparent functions in the context of obesity. Interest in ACE2 has become even greater with the discovery that it serves as the cell receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), opening up numerous mechanisms for deleterious effects of infection. The proliferation of ACE2 within the literature coupled with its dual role in SARS-CoV-2 infection and obesity necessitates review of the current understanding of ACE2's physiological, pathophysiological, and potential therapeutic functions. This review highlights the roles of ACE2 in cardiac dysfunction and obesity, with focus on epicardial adipose tissue, to reconcile the data in the context of SARS-CoV-2 infection.

The role of angiotensin-converting enzyme 2 in coronaviruses/influenza viruses and cardiovascular disease.

Angiotensin-converting enzyme 2 (ACE2) has emerged as a key regulator of the renin-angiotensin system in cardiovascular (CV) disease and plays a pivotal role in infections by coronaviruses and influenza viruses. The present review is primarily focused on the findings to indicate the role of ACE2 in the relationship of coronaviruses and influenza viruses to CV disease. It is postulated that the risk of coronavirus or influenza virus infection is high, at least partly due to high ACE2 expression in populations with a high CV risk. Coronavirus and influenza virus vaccine usage in high CV risk populations could be a potential strategy to prevent both CV disease and coronavirus/influenza virus infections.

The Effect of Coronavirus Disease 2019 on Cardiovascular Diseases. / O Efeito da Doença de Coronavírus 2019 nas Doenças Cardiovasculares.

Coronavirus disease 2019 (COVID-19) is a global pandemic affecting the world, seen in more than 1,300,000 patients. COVID-19 acts through the angiotensin-converting enzyme 2 (ACE2) receptor. Cardiovascular comorbidities are more common with COVID-19, and nearly 10% of cases develop myocarditis (22% of critical patients). Further research is needed to continue or discontinue ACE inhibitors and angiotensin receptor blockers, which are essential in hypertension and heart failure in COVID-19. Intensive research is promising for the treatment and prevention of COVID-19.

A doença de coronavírus 2019 (COVID-19) é uma pandemia global afetando o mundo, estando presente em mais de 1.300.000 pacientes. O COVID-19 age pelo receptor da enzima conversora de angiotensina 2 (ECA2). As comorbidades cardiovasculares são mais frequentes com COVID-19, e cerca 10% de casos desenvolvem miocardite (22% de pacientes críticas). Mais pesquisas serão necessárias para continuar ou descontinuar inibidores de ECA e bloqueadores dos receptores da angiotensina, que são essenciais para hipertensão e insuficiência cardíaca em COVID-19. Pesquisa intensiva é promissora para o tratamento e a prevenção da COVID-19.

Is amiloride a promising cardiovascular medication to persist in the COVID-19 crisis?

In the ongoing coronavirus diseases-2019 (COVID-19) crisis that caused immense suffering and deaths, the choice of therapy for the prevention and life-saving conditions must be based on sound scientific evidence. Uncertainty and apprehension are exacerbated in people using angiotensin-converting enzyme (ACE) inhibitors to control their comorbidities such as hypertension and diabetes. These drugs are reported to result in unfavorable outcome as they tend to increase the levels of ACE2 which mediates the entry of SARS-CoV-2. Amiloride, a prototypic inhibitor of epithelial sodium channels (ENaC) can be an ideal candidate for COVID-19 patients, given its ACE reducing and cytosolic pH increasing effects. Moreover, its potassium-sparing and anti-epileptic activities make it a promising alternative or a combinatorial agent.

COVID-19, ACE2, and the cardiovascular consequences.

The novel SARS coronavirus SARS-CoV-2 pandemic may be particularly deleterious to patients with underlying cardiovascular disease (CVD). The mechanism for SARS-CoV-2 infection is the requisite binding of the virus to the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) and internalization of the complex by the host cell. Recognition that ACE2 is the coreceptor for the coronavirus has prompted new therapeutic approaches to block the enzyme or reduce its expression to prevent the cellular entry and SARS-CoV-2 infection in tissues that express ACE2 including lung, heart, kidney, brain, and gut. ACE2, however, is a key enzymatic component of the renin-angiotensin-aldosterone system (RAAS); ACE2 degrades ANG II, a peptide with multiple actions that promote CVD, and generates Ang-(1-7), which antagonizes the effects of ANG II. Moreover, experimental evidence suggests that RAAS blockade by ACE inhibitors, ANG II type 1 receptor antagonists, and mineralocorticoid antagonists, as well as statins, enhance ACE2 which, in part, contributes to the benefit of these regimens. In lieu of the fact that many older patients with hypertension or other CVDs are routinely treated with RAAS blockers and statins, new clinical concerns have developed regarding whether these patients are at greater risk for SARS-CoV-2 infection, whether RAAS and statin therapy should be discontinued, and the potential consequences of RAAS blockade to COVID-19-related pathologies such as acute and chronic respiratory disease. The current perspective critically examines the evidence for ACE2 regulation by RAAS blockade and statins, the cardiovascular benefits of ACE2, and whether ACE2 blockade is a viable approach to attenuate COVID-19.

COVID-19: A Concern for Cardiovascular Disease Patients.

Coronavirus disease 2019 (COVID-19) is declared as a pandemic that has spread worldwide, affecting 205 countries. The disease affected 1, 40, 43, 176 individuals and caused 5, 97, 583 deaths around the globe. The organism responsible for the cause of disease is Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). SARS-CoV-2 enters into the cell via receptors present on the cell surface named angiotensin-converting enzyme 2 (ACE2) receptor. Notwithstanding ACE2 receptors acts as a gateway for infection, and most of the cardiovascular patients are treated with the ACE inhibitors. Thus, the role of ACE inhibitors or angiotensin receptor blockers may play a critical role in the severity or outcome of disease. Also, the effect of ACE inhibitors varies with the polymorphism in ACE2 receptors present in the individuals. Hence, it is the need of the hour to investigate the mechanisms which could better aid in the treatment of COVID-19-infected cardiovascular disease (CVD) patients.