Biology subjects

Shah, S. T. A.

Publications and source records attributed to Shah, S. T. A..

2 recordsLinked to original sources

bioRxiv2019

Animal model and therapeutic prospects for left ventricular hypertrophy and associated renal complication

Cardiac and renal dysfunction often co-occur and considerably worsen the prognosis leading to difficulty in therapy in left ventricular hypertrophy (LVH). The aim of this study was to elucidate changes in expression of human ortholog genes of hypertension, vascular and cardiac remodeling and hypertensive nephropathy phenotypes under normal, disease and gasotransmitter, H2S (hydrogen sulphide) and NO (nitric oxide) and combined (H2S+NO), treatment of rat myocardium and renal tissues. LVH rat models were generated and were treated with H2S and NO. Relative gene expression was quantified. Heart and renal physical indices were significantly modified under individual as well as combined H2S+NO treatment in control and LVH rats. Expression analysis revealed, hypertension, vascular remodeling genes ACE, TNF and IGF1, mRNAs to be significantly increased (P<0.05) in myocardia and kidneys of LVH rats, while individual and combined H2S+NO treatment reduced gene expression to normal/near to normal values. The cardiac remodeling genes MYH7, TGF{beta}, SMAD4 and BRG1 expression were significantly up-regulated (P<0.05) in the myocardia of LVH and combined H2S+NO treatment, which recovered the normal/near to normal expression more effectively as compared to individual treatments. Interestingly, individual as well as combined H2S and NO treatment significantly decreased PKD1 expression in renal tissue, which was significantly up-regulated in LVH rats (P<0.05). The reduction in hemodynamic parameters and cardiac indices as well as alteration in gene expression on treatment in LVH rat model indicates important therapeutic potential of combined treatment with H2S+NO gasotransmitters in hypertension and cardiac hypertrophy associated with renal complications.

pharmacology and toxicology↗

bioRxiv2018

Modulation of ADARs mRNA expression in congenital heart defect patients

Adenosine (A) to inosine (I) RNA editing, is a hydrolytic deamination reaction catalyzed by adenosine deaminase (ADAR) acting on RNA enzymes. RNA editing is a molecular process that involves the post-transcriptional modification of RNA transcripts. Interestingly, few studies have been carried out to determine the role of RNA editing in vascular disease. The current study found that in blood samples positive for congenital heart disease (CHD) ADAR1 and ADAR2 expression change at RNA level was opposite to each other. That is, an increase of ADAR1 mRNA was noticed in human CHD cases, whereas ADAR2 mRNA was vastly down-regulated. The increase in ADAR1 may be explained by the stress induced by CHD. The dramatic decrease in ADAR2 in CHD cases was unexpected and prompted further investigation into its effects on the heart. Therefore we performed expression analysis on a microarray data encompassing ischemic and non-Ischemic cardiomyopathy patient myocardial tissues. A strong down-regulation of ADAR2 was observed in both ischemic and especially non-ischemic cases. However, ADAR1 showed a mild increase in the case of non-ischemic myocardial tissues. To further explore the role of ADAR2 with respect to heart physiology. We selected a protein coding gene filamin B (FLNB). FLNB is known to play an important role in heart development. Although there were no observable changes in its expression, the editing levels of FLNB dropped dramatically in ADAR2-/- mice. We also performed miRNA profiling from ADAR2 -/- mice heart tissue revealed a decrease in expression of miRNAs. It is established that aberrant expression of these miRNAs is often associated with cardiac defects. This study proposes that sufficient amounts of ADAR2 might play a vital role in preventing cardiovascular defects.

molecular biology↗