Update on RAAS Modulation for the Treatment of Diabetic Cardiovascular Disease

Abstract

Since the advent of insulin, the improvements in diabetes detection and the therapies to treat hyperglycemia have reduced the mortality of acute metabolic emergencies, such that today chronic complications are the major cause of morbidity and mortality among diabetic patients. More than half of the mortality that is seen in the diabetic population can be ascribed to cardiovascular disease (CVD), which includes not only myocardial infarction due to premature atherosclerosis but also diabetic cardiomyopathy. The importance of renin-angiotensin-aldosterone system (RAAS) antagonism in the prevention of diabetic CVD has demonstrated the key role that the RAAS plays in diabetic CVD onset and development. Today, ACE inhibitors and angiotensin II receptor blockers represent the first line therapy for primary and secondary CVD prevention in patients with diabetes. Recent research has uncovered new dimensions of the RAAS and, therefore, new potential therapeutic targets against diabetic CVD. Here we describe the timeline of paradigm shifts in RAAS understanding, how diabetes modifies the RAAS, and what new parts of the RAAS pathway could be targeted in order to achieve RAAS modulation against diabetic CVD.

A Case of Novel Coronavirus Disease 19 in a Chronic Hemodialysis Patient Presenting with Gastroenteritis and Developing Severe Pulmonary Disease

“…Prior studies suggested that angiotensin-converting enzyme 2 (ACE2)-binding capacity is strongly associated with coronavirus infectivity and disease severity. ACE2 may be differentially upregulated by ACEi, ARB, and aldosterone antagonists [12][13][14]. It is postulated that the expression of ACE2 may be increased with the use of ACEi, ARB, and aldosterone antagonists, particularly in diabetic patients, and therefore it has been suggested that increased expression of ACE2 may facilitate infection by COVID-19.…”

The role of spironolactone on myocardial oxidative stress in rat model of streptozotocin‐induced diabetes

“…Angiotensin‐II (Ang‐II) is produced by cardiac myocytes and fibroblasts in response to hemodynamic stresses, and Ang‐II‐dependent and Ang‐II‐independent cascades are activated in hypertension, heart failure (HF), and other conditions . The mineralocorticoid aldosterone is a key component of the renin–angiotensin–aldosterone system (RAAS), produced by aldosterone synthase .…”

“…The RAAS contributes to the etiology of CVD and diabetes . In patients with type I diabetes, plasma levels of renin, Ang‐II, and aldosterone are elevated .…”

Glucagon‐like peptide‐1 ameliorates cardiac lipotoxicity in diabetic cardiomyopathy via the PPARα pathway

“…Cardiovascular events account for two‐thirds of the mortality in patients with diabetes (Boudina & Abel, 2007). Diabetic cardiomyopathy (DCM) is a major cardiovascular complication (Bernardi, Michelli, Zuolo, Candido & Fabris, 2016). DCM is defined as structural and functional myocardial impairments in diabetic patients without coronary artery disease or hypertension.…”