Oleanolic acid and ursolic acid induce hypertrophy in neonatal rat ventricular cardiomyocytes.

Hannaneh Parvaresh,1 Zeinab neshati,2,*

1. 1. Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
2. 1. Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran 2. Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran

Abstract


Introduction

The major function of the heart is to maintain perfusion of peripheral organs during both normal and stress conditions. in response to an increased workload, the heart and the individual cardiomyocytes often undergo enlargement. this condition termed hypertrophy. cardiac hypertrophy increases contractility and left ventricular wall thickness, thereby maintaining cardiac efficiency. cardiac hypertrophy is also accompanied by some changes, such as, changes in gene expression, increased cell size, increased cell protein and rna content and increased production and assembly of contractile proteins into sarcomeric units, which induce changes in metabolism, contractility and cardiomyocyte survival. there are two types of cardiac hypertrophy: physiological and pathological hypertrophy. development of either physiological or pathological hypertrophy depends on the nature of upstream stimuli and signaling mechanisms. stimuli inducing physiological hypertrophy often reverse the progression of pathological hypertrophy to cardiac remodeling and heart failure. oleanolic acid (3′-hydroxy-olea-12-en-28-oic acid) and its isomer, ursolic acid (3′-hydroxy-urs-12-en-28-oic-acid), are triterpenoid compounds that exist largely in vegetable oils, and in more than 120 plant species, many of them are used in traditional medicine. since previous studies have demonstrated that oleanolic acid (oa) and ursolic acid (ua) attenuate pathological cardiac hypertrophy in vivo induced by aortic banding and transverse aortic constriction surgery, in this study, we examined the induction of physiological cardiac hypertrophy in vitro by oa and ua as a mechanism of such observations.

Methods

: neonatal rat ventricular cardiomyocytes (nrcmcs) were isolated from 2-day-old animals and cultured as confluent monolayers. cells were treated with 5 μg/ml of oa and ua at day 3 and day 5 after culture initiation. induction of hypertrophic response was examined by analysis of cell surface area and protein content at 7th day.

Results

We observed that oleanolic acid and ursolic acid did not have any cytotoxic effects on cells and they could increase protein content and cell surface area of nrcmcs, 1.5 - 2 fold more than the control group, suggesting that these agents induce hypertrophy.

Conclusion

Increase in protein content and cell surface area of nrcmcs indicate oleanolic and ursolic acid induce cardiac hypertrophy. however, investigation of gene expression pattern is necessary for determination of the nature of hypertrophy. in the case of the induction of physiological hypertrophy, oleanolic acid and ursolic acid might serve as new therapeutic agents for pathological hypertrophy. increase in protein content and cell surface area of nrcmcs indicate oleanolic and ursolic acid induce cardiac hypertrophy. however, investigation of gene expression pattern is necessary for determination of the nature of hypertrophy. in the case of the induction of physiological hypertrophy, oleanolic acid and ursolic acid might serve as new therapeutic agents for pathological hypertrophy.

Keywords

: hypertrophy – neonatal rat ventricular cardiomyocytes – oleanolic acid – ursolic acid