Altara Raffaele, Giordano Mauro, Nordén Einar S, Cataliotti Alessandro, Kurdi Mazen, Bajestani Saeed N, Booz George W
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.
KG Jebsen Center for Cardiac Research, Oslo, Norway.
Front Endocrinol (Lausanne). 2017 Jul 17;8:160. doi: 10.3389/fendo.2017.00160. eCollection 2017.
Heart failure with preserved ejection fraction (HFpEF) is a major unmet medical need that is characterized by the presence of multiple cardiovascular and non-cardiovascular comorbidities. Foremost among these comorbidities are obesity and diabetes, which are not only risk factors for the development of HFpEF, but worsen symptoms and outcome. Coronary microvascular inflammation with endothelial dysfunction is a common denominator among HFpEF, obesity, and diabetes that likely explains at least in part the etiology of HFpEF and its synergistic relationship with obesity and diabetes. Thus, pharmacological strategies to supplement nitric oxide and subsequent cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling may have therapeutic promise. Other potential approaches include exercise and lifestyle modifications, as well as targeting endothelial cell mineralocorticoid receptors, non-coding RNAs, sodium glucose transporter 2 inhibitors, and enhancers of natriuretic peptide protective NO-independent cGMP-initiated and alternative signaling, such as LCZ696 and phosphodiesterase-9 inhibitors. Additionally, understanding the role of adipokines in HFpEF may lead to new treatments. Identifying novel drug targets based on the shared underlying microvascular disease process may improve the quality of life and lifespan of those afflicted with both HFpEF and obesity or diabetes, or even prevent its occurrence.
射血分数保留的心力衰竭（HFpEF）是一项尚未满足的重大医疗需求，其特征是存在多种心血管和非心血管合并症。这些合并症中最主要的是肥胖和糖尿病，它们不仅是HFpEF发生的危险因素，还会使症状恶化并影响预后。伴有内皮功能障碍的冠状动脉微血管炎症是HFpEF、肥胖和糖尿病的共同特征，这可能至少部分解释了HFpEF的病因及其与肥胖和糖尿病的协同关系。因此，补充一氧化氮以及随后的环磷酸鸟苷（cGMP）-蛋白激酶G（PKG）信号传导的药理学策略可能具有治疗前景。其他潜在方法包括运动和生活方式改变，以及靶向内皮细胞盐皮质激素受体、非编码RNA、钠-葡萄糖协同转运蛋白2抑制剂，以及利钠肽保护性非一氧化氮依赖性cGMP启动和替代信号传导的增强剂，如LCZ696和磷酸二酯酶-9抑制剂。此外，了解脂肪因子在HFpEF中的作用可能会带来新的治疗方法。基于共同的潜在微血管疾病过程确定新的药物靶点，可能会改善同时患有HFpEF和肥胖或糖尿病的患者的生活质量和寿命，甚至预防其发生。
