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Research Interests

With changing life style and food habits, hypertension has become quite prevalent. Our group is focussing on the pathophysiology of hypertension. The question which motivates us is how hypertension, apart from severe vasoconstriction, causes target organ damage. We are trying to understand the molecular mechanism behind the damage of lungs, brain and vasculature caused by severe and persistently elevated blood pressure.

Increase in the blood pressure due to severe pulmonary vasoconstriction results in Pulmonary Hypertension (PH). This disease is prevalent in patients of chronic obstructive pulmonary diseases (COPD) and congestive heart failure. PH afflicts natives and army persons working at high altitude like Himalayan region. Apart from severe vasoconstriction, there is lot of pulmonary vascular remodelling, apoptosis resistance, altered metabolism and DNA damage in the lungs. Our studies have shown increased de novo fatty acid synthesis (Fatty acid Synthase, FAS) and activation of DNA repairing enzymes like PARP-1. Having a deeper understanding of altered metabolism and DNA repairing may shed light on how diseases develop, which in turn may lead to new methods of diagnosis and therapy.

Another organ which gets affected by severe hypertension is brain. In rat model of renovascular hypertension we found activation of astrocytes and microglia (brain cells). This activation resulted in inflammation, apoptosis and oxidative stress in brain of hypertensive rats. Our flow cytometry and Immunocytochemistry studies also showed the deposition of platelets which lead to the activation of inflammatory CD 40 signalling, TRAF, ERK1/2 and MAP kinase signalling. Our studies in hypertensive rats showed that certain antihypertensive agents, apart from lowering blood pressure, may also have neuroprotective effects.

Another area where we have diverted our attention is role of Autophagy in chronic hypertension. Autophagy, meaning self digestion, is a conserved event which takes place when cell is under stress. Stressed cells digest their organelle like mitochondria so that released amino acids, carbohydrates, lipids can be used for survival. Hypertension is also a stressful condition but role of autophagy has not been much explored. We are investigating role of LC3B and p62, the prominent markers of autophagy, in in vitro conditions and rat model of renovascular hypertension