Hypertension induced target organ damage: Effect of chronic hypertension on lungs, brain and vasculature

Pulmonary hypertension: Study on the role of DNA repairing enzymes and de novo Fatty acid synthesis

Pulmonary hypertension (PH) is a progressive occlusive vasculopathy in the lungs leading to increased pulmonary arterial pressure and resulting in right ventricle hypertrophy and heart failure. Patients of Chronic obstructive pulmonary disease (COPD), chronic heart diseases and large number of sojourners and army persons at high altitude, suffer from PH. Apart from severe pulmonary vasoconstriction, pulmonary vascular remodelling, endothelial dysfunction, cardiac dysfunction are involved in the pathophysiology of PH. PH shows deregulated angiogenesis, high expression of cellular growth factors, imbalance between proliferation and apoptosis, and altered energy metabolism. Our studies have suggested that metabolic dysfunctions and DNA damage play major role in progression of PH. . Therefore, we are focussing on the role of DNA repairing enzymes, Poly (ADP-Ribose) Polynerase-1 (PARP-1), and do novo fatty acid synthesis enzyme, Fatty Acid Synthase (FAS) in PH. We are using pulmonary artery smooth muscle cells, pulmonary artery endothelial cells and cardiomyocytes culture to elucidate the mechanism involved in pulmonary smooth muscle cells remodelling, endothelial dysfunction and cardiac dysfunction in PH progression. Further, we are validating our findings in a rat model of monocrotaline induced PH to study the DNA damage and altered lipid metabolism in PH.

1. Singh N, Manhas A, Kaur G, Jagavelu K, Hanif K. Inhibition of Fatty Acid Synthase is Protective in Pulmonary Hypertension. Br J Pharmacol. 2016 Apr7.doi: 10.1111/bph.1349
2 Kaur G, Singh N, Lingeshwar P, Siddiqui HH, Hanif K Poly (ADP-ribose) polymerase-1: an emerging target in right ventricle dysfunction associated with pulmonary hypertension. Pulm Pharmacol Ther. 2015 Feb;30:66-79.