Micro RNA and Cardiovascular
Cardiovascular disease is the leading cause of deaths worldwide and is one of the main causes of morbidity and mortality in developed countries. The pathological process of the heart is related to altered expression of genes that are important for cardiac function. Thus micro RNAs have become known as key regulators of gene expression and the recent studies have suggested the potential importance of micro RNAs as diagnostic markers and therapeutic targets for many big diseases including cardiac diseases. Deregulated expression of micro RNA has been linked to the development of cardiovascular disease.
The regulation of cardiovascular development requires specific control of gene expression and heterozygous mutations of transcription factors have frequently been implicated in cardiovascular abnormalities. A novel mechanism involving post-transcriptional regulation by micro RNAs (mRNAs) has emerged as a central regulator of many cardiogenic processes. The researchers are beginning to understand the functions that micro RNAs play during cell proliferation, differentiation, apoptosis, stress response and formation of tumour. The identification of micro RNAs expressed in specific cardiac and vascular cell types has led to the discovery of important regulatory roles for these small RNAs during cardiac muscle differentiation, cell cycle, conduction and vessel formation.
1. Cardiac Hypertrophy
An experiment done to investigate the potential involvement of micro RNAs in cardiac hypertrophy….
Performed a micro RNA microarray analysis in two mouse models using a microarray that represented 186 different micro RNAs. In one model, mice were subjected to thoracic aortic banding (TAB) and were compared with the control (40). In a second model, Tg mice expressing activated calcineurin A in the heart were compared with WT littermates (41). TAB and can induce hypertrophy (42, 43).
RNA isolated from hearts of mice in the first study showed increased expression of 27 micro RNAs and decreased expression of 15 microRNAs compared to the control. Mice from the second study showed increased expression of 33 micro RNAs and decreased expression of 14 microRNAs respectively (43).
Northern blot (43)analysis of both studies confirmed an increased expression of micro RNA-21, micro RNA-23, micro RNA-24, micro RNA-125b, micro RNA-195, micro RNA-199a and micro RNA-214 (43) and reduced expression of micro RNA-29c, micro RNA-93, micro RNA-150, and micro RNA-181b. These data indicate that marked micro RNAs are regulated during cardiac hypertrophy, suggesting the possibility that they might perform as regulator of this process.
Ventricular hypertrophy often leads to heart failure in humans (44). Northern blot analysis of the micro RNAs in end stage failing human hearts showed increased expression of micro RNA-24, micro RNA-125b, micro RNA-195, micro RNA-199a and micro RNA-214 (43). The changed pattern of micro RNA expression in the end stage failing...