Sciarretta Sebastiano, Paneni Francesco, Palano Francesca, Chin Diana, Tocci Giuliano, Rubattu Speranza, Volpe Massimo
Department of Cardiology, II Faculty of Medicine, University of Rome La Sapienza, S. Andrea Hospital, Via di Grottarossa 1035-1039, 00100 Rome, Italy.
Clin Sci (Lond). 2009 Mar;116(6):467-77. doi: 10.1042/CS20080390.
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.
左心室舒张功能障碍是一种常见的临床病症，与心血管疾病发病率和死亡率的增加相关。舒张功能障碍是射血分数保留的心力衰竭（HF-PSF）最常见的原因。因此，了解舒张功能障碍的病理生理机制以及能够对抗其发展和进展的有效治疗策略变得至关重要。在可能导致舒张功能障碍发展的复杂病理生理因素中，肾素-血管紧张素-醛固酮系统（RAAS）已被证明发挥重要作用。RAAS的旁分泌和自分泌信号促进心脏的结构和功能变化，这在很大程度上与心肌纤维化增加有关。RAAS活性增强和失调也有助于容量超负荷和血管收缩的发展，随后左心室舒张充盈压升高，发生充血性心力衰竭（CHF）的易感性增加。最近，也有人提出RAAS可能通过激活不同细胞类型以及分泌细胞因子和趋化因子在引发心肌和血管炎症中起作用。RAAS诱导的心肌炎症导致血管周围心肌纤维化以及舒张功能障碍的发生或进展。基于这些原因，RAAS的药理学阻断已被提议作为治疗舒张功能障碍的合理方法。事实上，血管紧张素转换酶抑制剂（ACEIs）、血管紧张素II受体阻滞剂（ARBs）和醛固酮拮抗剂（AAs）已被证明可延缓从临床前期舒张功能障碍向CHF的发展和进展，并降低与此病症相关的发病率和死亡率。
