Role of the renin–angiotensin–aldosterone system and inflammatory processes in the development and progression of diastolic dysfunction

Abstract

Left ventricular diastolic dysfunction represents a frequent clinical condition and is associated with increased cardiovascular morbidity and mortality. Diastolic dysfunction is the most common cause of HF-PSF (heart failure with preserved ejection fraction). Therefore it becomes important to understand the pathophysiological mechanisms underlying diastolic dysfunction, as well as the effective therapeutic strategies able to antagonize its development and progression. Among the complex pathophysiological factors that may contribute to the development of diastolic dysfunction, the RAAS (renin-angiotensin-aldosterone system) has been shown to play a significant role. Paracrine and autocrine signals of the RAAS promote structural and functional changes in the heart largely linked to increased myocardial fibrosis. Enhanced and dysregulated activity of the RAAS also contributes to the development of volume overload and vasoconstriction with subsequent increases in left ventricular diastolic filling pressures and a higher susceptibility of developing CHF (congestive heart failure). More recently, it has also been suggested that the RAAS may play a role in triggering myocardial and vascular inflammation through the activation of different cell types and the secretion of cytokines and chemokines. RAAS-induced myocardial inflammation leads to perivascular myocardial fibrosis and to the development or progression of diastolic dysfunction. For these reasons pharmacological blockade of the RAAS has been proposed as a rational approach for the treatment of diastolic dysfunction. In fact, ACEIs (angiotensin-converting enzyme inhibitors), ARBs (angiotensin II receptor blockers) and AAs (aldosterone antagonists) have been demonstrated to delay the development and progression from pre-clinical diastolic dysfunction towards CHF, as well as to reduce the morbidity and mortality associated with this condition.

Altered left ventricular diastolic function in subjects with spinal cord injury

“…6 Similarly, the development of LV diastolic dysfunction has been reported in individuals subjected to prolonged physical inactivity, 7,8 thereby suggesting that patients with SCI might be at a higher risk of developing abnormalities in LV function. The aim of this study was to investigate cardiac functional and structural parameters in SCI and able-bodied subjects and evaluate the impact of clinical, hemodynamic, metabolic and inflammatory variables in this regard.…”

Enalapril in Combination with Benznidazole Reduces Cardiac Inflammation and Creatine Kinases in Mice Chronically Infected with Trypanosoma cruzi

“…[8][9][10][11][12] ACE inhibitors have been shown to be efficacious not only as therapies against hypertension and protection against left ventricular hypertrophy but also in the regulation of the immune system related to distinct diseases, including the T. cruziinduced pathologies. 9,[13][14][15] Their actions are based on the angiotensin II, a key factor in the renin-angiotensin system that plays an essential role in the regulation of blood pressure, and that also interferes in the cardiac inflammatory activity through the activation of the nuclear factor kappaB (NF-κB) and in the production of inflammatory cytokines and chemokines. 16 In the context of the experimental T. cruzi infection, the ACE inhibitor captopril was previously demonstrated to be able to decrease the delayed-type hypersensitivity response against parasite in acute myocarditis.…”

Effects of Reduced Kidney Function Because of Living Kidney Donation on Left Ventricular Mass

“…[28][29][30] Indeed, our study shows adrenal gland hypertrophy and an increase of the aldosterone:renin ratio, 13,14 suggesting that sympathetic activation may be involved in the postnephrectomy hypertrophy of the heart and remnant kidney. Although an activation of the renin-aldosterone system has been shown in patients with chronic kidney disease, 8,31 adrenal hypertrophy has been described only in animal studies. 29,32 Further, aging is an unlikely mechanism of development of LVM because echocardiographic studies in the healthy general population have shown that there is no increase of LVM with age after adjusting for body surface area.…”