title: The correlation between angiogenesis and abnormal expression of SERCA2a, phospholamban and the endothelin pathway in heart failure, and improvement by puerarin.
abstract: Emerging evidence indicates that angiogenesis may be a potential new target in treating heart failure (HF). It was hypothesized that a lack of angiogenesis would correlate with an abnormal expression of sarco/endoplasmic reticulum ATPase 2a (SERCA2a) and phospholamban (PLB), and the activated endothelin (ET) pathway and oxidative stress in HF. If this is the case, such normal changes could be reversed by puerarin. HF was produced by coronary artery ligation for 4 weeks in rats. The rats were divided into three groups: sham, HF untreated and HF + puerarin (120 mg/kg per day, i.p.). Hemodynamic and echocardiographic changes, angiogenesis, cardiac morphology, serum biochemistry, mRNA and proteins of the angiogenesis pathway, the ET pathway and redox were measured. In the HF rats, hemodynamic and echocardiographic abnormalities, cardiac remodeling and histological changes with features of cardiac failure were associated with a lack of the angiogenesis pathway, accompanied by oxidative stress, an up-regulated ET pathway and abnormal SERCA2a and PLB expressions in HF rats. Puerarin significantly promoted angiogenesis and reversed the above changes. In conclusion, the absence of the angiogenesis pathway correlated with abnormal expression of SERCA2a and PLB and an activated ET-ROS (reactive oxygen species) system in the affected myocardium. Puerarin promoted the angiogenesis pathway, improved myocardial microcirculation and down-regulated the ET system, resulting in a reversal of the abnormalities of expression of SERCA2a and PLB, and the cardiac performance in HF.
authors.affiliation: Institute of Chinese Herbal Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: He
authors.forename: Mengqiong
authors.initials: M
authors.lastname: Shi
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zeng
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Qiao
authors.forename: Limao
authors.initials: L
authors.lastname: Wu
authors.forename: Lianda
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003331:Coronary Vessels / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D016232:Endothelins / Q000235:genetics / Q000378:metabolism*; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D007529:Isoflavones / Q000627:therapeutic use*; D009206:Myocardium / Q000201:enzymology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D014665:Vasodilator Agents / Q000627:therapeutic use*; D020257:Ventricular Remodeling / Q000187:drug effects; D000099211:Phospholamban
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; D016232:Endothelins; D007529:Isoflavones; D011506:Proteins; D017382:Reactive Oxygen Species; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D014665:Vasodilator Agents; D000099211:Phospholamban; C506948:Atp2a2 protein, rat; C033607:puerarin