Kafait U. Malik, Ph.D., D.Sc., Professor
Department of Pharmacology

The focus of our research is to investigate the mechanism of interaction of the adrenergic nervous system, angiotensin II (Ang II) and eicosanoids in the regulation of vascular injury (hyperplasia, hypertrophy) and development of hypertension. Norepinephrine (NE), adrenergic neurotransmitter and ANG II stimulate calcium/calmodulin dependent protein kinase II (CaMKII) that phosphorylate phospholipase A2 (cPLA2) and release arachidonic acid (AA) in vascular smooth muscle cells (VSMC); AA metabolites formed via cytochrome p450 (CYP-450) and lipoxygenase (LO) activate phospholipase D (PLD), amplify cPLA2 activity and contribute to VSMC hyperplasia, hypertrophy and hypertension. We are now investigating the mechanism by which ANG II and NE produce vascular injury through AA metabolites. Our recent studies indicate that ANGII promote VSMC proliferation in balloon injured rat carotid artery via activation of PKC zeta. We are now examining the contribution of PKC zeta to vascular injury produced by AA and its metabolites.

Recent Publications

Norepinephrine-induced stimulation of p38 Mitogen-activated protein kinase is mediated by arachidonic acid metabolites generated by activation of cytosolic phospholipase A2 in vascular smooth muscle cells. Kalyankrishna S and Malik KU. Journal of Pharmacology and Experimental Therapeutics 304:761-772, 2003.

CaM kinase II alpha mediates norepinephrine-induced translocation of cytosolic phospholipase A2 to the nuclear envelope. Fatima S, Yaghini FA, Ahmed A, Khandekar Z and Malik KU. Journal of Cell Science 116:353-365, 2003.

Parmentier, J-H., Smelcer, P., Pavicevic, Z., Basic, E., Idrizovic, A., Estes, A and Malik, K.U. PKC-zeta mediates norepinephrine-induced phospholipase D activation and cell proliferation in VSMC. Hypertension 41(3 Pt 2):794-800, 2003.

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