Cornuault Lauriane, Rouault Paul, Duplàa Cécile, Couffinhal Thierry, Renault Marie-Ange
Univ. Bordeaux, INSERM, Biology of Cardiovascular Diseases, U1034, Pessac, France.
Front Physiol. 2022 Jul 8;13:906272. doi: 10.3389/fphys.2022.906272. eCollection 2022.
Heart failure with preserved ejection fraction (HFpEF) has been recognized as the greatest single unmet need in cardiovascular medicine. Indeed, the morbi-mortality of HFpEF is high and as the population ages and the comorbidities increase, so considerably does the prevalence of HFpEF. However, HFpEF pathophysiology is still poorly understood and therapeutic targets are missing. An unifying, but untested, theory of the pathophysiology of HFpEF, proposed in 2013, suggests that cardiovascular risk factors lead to a systemic inflammation, which triggers endothelial cells (EC) and coronary microvascular dysfunction. This cardiac small vessel disease is proposed to be responsible for cardiac wall stiffening and diastolic dysfunction. This paradigm is based on the fact that microvascular dysfunction is highly prevalent in HFpEF patients. More specifically, HFpEF patients have been shown to have decreased cardiac microvascular density, systemic endothelial dysfunction and a lower mean coronary flow reserve. Importantly, impaired coronary microvascular function has been associated with the severity of HF. This review discusses evidence supporting the causal role of endothelial dysfunction in the pathophysiology of HFpEF in human and experimental models.
射血分数保留的心力衰竭（HFpEF）已被公认为心血管医学中最大的单一未满足需求。事实上，HFpEF的发病率和死亡率都很高，而且随着人口老龄化和合并症增加，HFpEF的患病率也大幅上升。然而，HFpEF的病理生理学仍未得到充分理解，且缺乏治疗靶点。2013年提出的一种关于HFpEF病理生理学的统一但未经检验的理论认为，心血管危险因素会导致全身炎症，进而引发内皮细胞（EC）和冠状动脉微血管功能障碍。这种心脏小血管疾病被认为是导致心脏壁僵硬和舒张功能障碍的原因。这一范式基于微血管功能障碍在HFpEF患者中高度普遍这一事实。更具体地说，HFpEF患者的心脏微血管密度降低、全身内皮功能障碍且平均冠状动脉血流储备较低。重要的是，冠状动脉微血管功能受损与HF的严重程度相关。本综述讨论了支持内皮功能障碍在人类和实验模型中HFpEF病理生理学中因果作用的证据。
