title: Protective Effect of RA on Myocardial Infarction-Induced Cardiac Fibrosis via AT1R/p38 MAPK Pathway Signaling and Modulation of the ACE2/ACE Ratio.
abstract: Rosmarinic acid (α-o-caffeoyl-3,4-dihydroxyphenyllactic acid, RA) is a major active constituent of Rosmarinus officinalis Linn. (rosemary) having significant anti-inflammatory, anti-apoptotic, and antioxidant effects. However, the cardioprotection of RA is still not understood. The present study was designed, for the first time, to investigate the cardioprotection of RA on myocardial infarction (MI)-induced cardiac fibrosis and to clarify the possible mechanisms. MI was induced in adult rats by left anterior descending coronary artery ligation, and animals were then administered RA (50, 100, or 200 mg/kg) by gavage. Compared with the model group, RA treatment ameliorated changes in the left ventricular systolic pressure (LVSP), +dp/dtmax, and -dp/dtmax after 4 weeks. This was associated with attenuation of infarct size, collagen volume fraction (CVF), expression of collagen I, collagen III, alpha smooth muscle actin (α-SMA), and hydroxyproline (Hyp) concentrations. RA treatment was also associated with decreased angiotensin-converting enzyme (ACE) expression and increased ACE2 expression, as well as decreased expression of angiotensin type 1 receptor (AT1R) and phospho-p38 mitogen-activated protein kinase (p38 MAPK). Thus, RA can protect against cardiac dysfunction and fibrosis following MI, likely due to decreasing ACE expression and increasing ACE2 expression via the AT1R/p38 MAPK pathway.
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University , Yantai 264005, P.R. China.
authors.forename: Qiaofeng
authors.initials: Q
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University , Yantai 264005, P.R. China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Tian
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University , Yantai 264005, P.R. China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University , Yantai 264005, P.R. China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Li
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University , Yantai 264005, P.R. China.
authors.forename: Xiangjing
authors.initials: X
authors.lastname: Meng
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University , Yantai 264005, P.R. China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Fu
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002934:Cinnamates / Q000008:administration & dosage*; D053630:Depsides / Q000008:administration & dosage*; D005355:Fibrosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D027542:Rosmarinus / Q000737:chemistry*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000097123:Rosmarinic Acid
chemical_list: D000085962:Angiotensin-Converting Enzyme 2; D002934:Cinnamates; D053630:Depsides; D007703:Peptidyl-Dipeptidase A; D010936:Plant Extracts; D044140:Receptor, Angiotensin, Type 1; D048051:p38 Mitogen-Activated Protein Kinases; D000097123:Rosmarinic Acid; C000705307:ACE2 protein, human; C000705329:Ace2 protein, rat
keywords: ACE; ACE2; AT1R/p38 MAPK; RA; cardiac dysfunction; cardiac fibrosis