ABSTRACT
The coronavirus disease (COVID-19) pandemic is a global health priority. Given that cardiovascular diseases (CVD) are the leading cause of morbidity around the world and that several trials have reported severe cardiovascular damage in patients infected with SARS-CoV-2, a substantial number of COVID-19 patients with underlying cardiovascular diseases need to continue their medications in order to improve myocardial contractility and to prevent the onset of major adverse cardiovascular events (MACEs), including heart failure. Some of the current life-saving medications may actually simultaneously expose patients to a higher risk of severe COVID-19. Angiotensin-converting enzyme 2 (ACE2), a key counter regulator of the renin-angiotensin system (RAS), is the main entry gate of SARS-CoV-2 into human host cells and an established drug target to prevent heart failure. In fact, ACE inhibitors, angiotensin II receptor blockers, and mineralocorticoid antagonists may augment ACE2 levels to protect organs from angiotensin II overload. Elevated ACE2 expression on the host cell surface might facilitate viral entrance, at the same time sudden nonadherence to these medications triggers MACEs. Hence, safety issues in the use of RAS inhibitors in COVID-19 patients with cardiac dysfunction remain an unsolved dilemma and need paramount attention. Although ACE2 generally plays an adaptive role in both healthy subjects and patients with systolic and/or diastolic dysfunction, we conducted a literature appraisal on its maladaptive role. Understanding the exact role of ACE2 in COVID-19 patients at risk of heart failure is needed to safely manage RAS inhibitors in frail and non-frail critically ill patients.
Subject(s)
Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme Inhibitors/adverse effects , COVID-19/chemically induced , COVID-19/epidemiology , Heart Failure/drug therapy , Angiotensin-Converting Enzyme 2/physiology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Humans , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/physiology , Risk AssessmentABSTRACT
PURPOSE: The effects of lithium (Li) and Valproic Acid (VA) drugs have been recently revealed to improve the Mesenchymal stem cells')MSCs (migration and proliferation processes. The aim of this study is to determine the expression of the genes involved in the proliferation and migration of limbal epithelial stem/progenitor cells (LESPCs) after treatment with Li and VA. METHODS: After extraction of LSCs from human Corneoscleral tissue, cells were subcultured three times. The cell culture media were divided into four separate groups including groups treated with VA, Li, combination, and control groups after determining the non-toxic concentration of drugs (64mml) Li and (28mml) VA based on MTT assay, and then cells cultures were treated for 3 hours. A real-time polymerase chain reaction was performed to detect the expression levels of CD44, Ki67, CXCR4, CXCR7, MMP-2, MMP-9, and SDF-1 genes. Changes in the expression of each gene in different treatments were calculated. Finally, the graphs were analyzed by SPSS (Version 18) software. RESULTS: The highest expression of CXCR4 and CXCR7 was in the Li-treated group. Additionally, the highest expression levels of MMP-9 and CD44 genes were observed in the VA-treated group. In contrast, the expression level of SDF-1a, MMP2, and Ki67 genes in all three treatment groups reduced compared to the control group. CONCLUSION: Increasing the LSCs migration genes (CXCR4 and MMP9) was more evident than cell proliferation genes (Ki67). In sum, Li and VA can affect the process of proliferation and migration of LSCs in vitro.
