Alamandine attenuates long-term hypertension-induced cardiac fibrosis independent of blood pressure

Autor: Lan Wang, Chi Liu, Xi-Ru Chen, Peng Li
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Cancer Research
Cardiac fibrosis
Pyridines
cardiac fibrosis
renin-angiotensin system
Blood Pressure
Biochemistry
chemistry.chemical_compound
0302 clinical medicine
Fibrosis
Rats
Inbred SHR
Ejection fraction
Angiotensin II
Imidazoles
Articles
Hydralazine
Oncology
Matrix Metalloproteinase 9
030220 oncology & carcinogenesis
Molecular Medicine
Oligopeptides
medicine.drug
medicine.medical_specialty
hypertension
Heart Ventricles
Diastole
Cardiomegaly
Collagen Type I
03 medical and health sciences
Internal medicine
Genetics
medicine
Animals
Spontaneous hypertensive rat
Molecular Biology
Sirius Red
Antihypertensive Agents
business.industry
medicine.disease
Rats
Collagen Type I
alpha 1 Chain
030104 developmental biology
Blood pressure
Endocrinology
chemistry
vasoactive peptide
business
Proto-Oncogene Proteins c-akt
Zdroj: Molecular Medicine Reports
ISSN: 1791-3004
1791-2997
Popis: Cardiac fibrosis secondary to long‑term hypertension is known to promote cardiac dysfunction; however, few therapeutic agents are available for the treatment of this condition in clinical practice. The heptapeptide alamandine (Ala) has recently been identified as a component of the renin‑angiotensin system (RAS), which exerts a protective effect against cardiac hypertrophy; however, it is unknown whether Ala may also be useful for the treatment of cardiac fibrosis. In the present study, the potential therapeutic effects of Ala on long‑term hypertension‑induced cardiac fibrosis were investigated in an aged, spontaneous hypertensive rat model. Weekly blood pressure (BP) measurements revealed that daily Ala treatment significantly decreased the systolic, diastolic and mean arterial BP compared with the control. Of note, the observed reduction in BP in Ala‑treated animals markedly differed to that observed in rats treated with hydralazine (Hyd). Echocardiography further demonstrated that Ala treatment decreased the ratio of left ventricle mass to body weight, and alleviated structural and functional parameters associated with cardiac fibrosis, including left ventricular volume, ejection fraction and fractional shortening compared with the control and Hyd‑treated groups. Furthermore, Ala deceased the density of cardiac fibrosis, as assessed by Masson and Sirius red staining; reduced expression of fibrotic proteins, including connective tissue growth factor, collagen I (COL1A1) and matrix metalloproteinase 9, was also observed. In addition, Ala treatment further decreased the expression of angiotensin II‑induced fibrotic markers at the mRNA and protein levels in cultured cardiac fibroblasts; Ala‑mediated inhibition of COL1A1 expression and Akt phosphorylation was inhibited via the Mas‑related G protein receptor antagonist, PD123319. Collectively, the findings of the present study suggest that Ala is an effective anti‑hypertensive peptide that can attenuate cardiac dysfunction and fibrosis induced by chronic hypertension, independent of BP.
Databáze: OpenAIRE
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