Bonanni Alice, Vinci Ramona, d'Aiello Alessia, Grimaldi Maria Chiara, Di Sario Marianna, Tarquini Dalila, Proto Luca, Severino Anna, Pedicino Daniela, Liuzzo Giovanna
Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Department of Cardiovascular and Pneumological Sciences, Catholic University of Sacred Heart, 00168 Rome, Italy.
J Clin Med. 2023 Sep 9;12(18):5862. doi: 10.3390/jcm12185862.
Heart failure with preserved ejection fraction (HFpEF) is a complex and heterogeneous clinical syndrome. The prevalence is expected to increase in the coming years, resulting in heart failure with reduced ejection fraction (HFrEF). This condition poses a burden to the global health care system as the number of patients affected by this condition is constantly increasing due to a rising average lifespan. The absence of validated drugs effective in reducing hospitalization rates and mortality may reflect the impossibility of applying a one size fits all approach as in HFrEF, heading for a personalized approach. Available evidence demonstrated the link between collagen quantity and quality alterations, and cardiac remodeling. In the context of fibrosis, collagen cross-linking is strictly involved, displaying two types of mechanisms: enzymatic and non-enzymatic. In the murine model, enzymatic inhibition of fibrosis-inducing protease-activated receptor-1 (PAR1) and transforming growth factor (TGF)-β signaling appeared to reduce cardiac fibrosis. On the other hand, in the case of non-enzymatic cross-linking, sodium glucose co-transporter type 2 inhibitors (SGLT2is), appeared to counteract the deposition of advanced glycation end-products (AGEs), which in turn contributed to ventricular remodeling. In this review, we address the mechanisms associated with collagen alterations to identify potential targets of cardiac fibrosis in HFpEF patients.
射血分数保留的心力衰竭（HFpEF）是一种复杂且异质性的临床综合征。预计在未来几年其患病率将会上升，导致射血分数降低的心力衰竭（HFrEF）。由于平均寿命的延长，受这种疾病影响的患者数量不断增加，这种情况给全球医疗保健系统带来了负担。缺乏有效降低住院率和死亡率的经验证药物，这可能反映出无法像在HFrEF中那样采用一刀切的方法，而需要采用个性化方法。现有证据表明胶原蛋白数量和质量的改变与心脏重塑之间存在联系。在纤维化的背景下，胶原蛋白交联密切相关，表现出两种机制：酶促和非酶促。在小鼠模型中，对纤维化诱导的蛋白酶激活受体-1（PAR1）和转化生长因子（TGF）-β信号通路的酶促抑制似乎可减轻心脏纤维化。另一方面，在非酶促交联的情况下，2型钠葡萄糖共转运体抑制剂（SGLT2is）似乎可抵消晚期糖基化终产物（AGEs）的沉积，而AGEs反过来又会导致心室重塑。在本综述中，我们探讨与胶原蛋白改变相关的机制，以确定HFpEF患者心脏纤维化的潜在靶点。
