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Endoplasmic reticulum stress and focused drug discovery in cardiovascular disease. Yang Yiyuan,Zhou Qionglin,Gao Anbo,Chen Linxi,Li Lanfang Clinica chimica acta; international journal of clinical chemistry Endoplasmic reticulum (ER) is an intracellular membranous organelle involved in the synthesis, folding, maturation and post-translation modification of secretory and transmembrane proteins. Therefore, ER is closely related to the maintenance of intracellular homeostasis and the good balance between health and diseases. Endoplasmic reticulum stress (ERS) occurs when unfolded/misfolded proteins accumulate after disturbance of ER environment. In response to ERS, cells trigger an adaptive response called the Unfolded protein response (UPR), which helps cells cope with the stress. In recent years, a large number of studies show that ERS can aggravate cardiovascular diseases. ERS-related proteins expression in cardiovascular diseases is on the rise. Therefore, down-regulation of ERS is critical for alleviating symptoms of cardiovascular diseases, which may be used in the near future to treat cardiovascular diseases. This article reviews the relationship between ERS and cardiovascular diseases and drugs that inhibit ERS. Furthermore, we detail the role of ERS inhibitors in the treatment of cardiovascular disease. Drugs that inhibit ERS are considered as promising strategies for the treatment of cardiovascular diseases. 10.1016/j.cca.2020.01.031
Endoplasmic reticulum stress: A common pharmacologic target of cardioprotective drugs. European journal of pharmacology Despite the advances made in cardiovascular disease prevention, there is still substantial residual risk of adverse cardiovascular events. Contemporary evidence suggests that additional reduction in cardiovascular disease risk can be achieved through amelioration of cellular stresses, notably inflammatory stress and endoplasmic reticulum (ER) stress. Only two clinical trials with anti-inflammatory agents have supported the role of inflammatory stress in cardiovascular risk. However, there are no clinical trials with selective ER stress modifiers to test the hypothesis that reducing ER stress can reduce cardiovascular disease. Nevertheless, the ER stress hypothesis is supported by recent pharmacologic studies revealing that currently available cardioprotective drugs share a common property of reducing ER stress. These drug classes include angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, mineralocorticoid receptor blockers, β-adrenergic receptor blockers, statins, and select antiglycemic agents namely, metformin, glucagon like peptide 1 receptor agonists and sodium glucose cotransporter 2 inhibitors. Although these drugs ameliorate common risk factors for cardiovascular disease, such as hypertension, hypercholesterolemia and hyperglycemia, their cardioprotective effects may be partially independent of their principal effects on cardiovascular risk factors. Clinical trials with selective ER stress modifiers are needed to test the hypothesis that reducing ER stress can reduce cardiovascular disease. 10.1016/j.ejphar.2022.175221