Ismail LAHER (Vancouver, Canada)
Ismail Laher is a Professor in the Department of Pharmacology and Therapeutics of the Faculty of medicine at the University of British Columbia in Vancouver, Canada. His research focus is in understanding the regulation of vascular function in health and disease, as shown in the brief summary below:
• Myogenic regulation of resistance arteries: Myogenic tone in arteries is an important component of blood flow regulation and also in determination of blood pressure of the circulation. Although Baylis first described the myogenic activity of blood vessels in 1902, I provided the first mechanistic insights for this phenomenon: for example, that myogenic tone was mediated by protein kinase C (J Pharmacol Exp Ther, 242: 566-572, 1986; Biochem. Biophys. Res. Comm. 158: 58-62, 1989); that myogenic tone had a lower Ca2+ requirement than other forms of vascular tone (Circ. Res. 63: 669-672, 1988; J. Hypertension 7: 517-520, 1989); myogenic activity is highly reliant on conducted communications between cells in the media using gap junctions (Am. J. Physiol. 283:H177-H2186, 2002).
• Resistance artery dysregulation in disease: Our laboratory reported reduced myogenic tone in coronary transplant vascular disease results from two main causes: increased iNOS expression and apoptosis of smooth muscle cells. The functional change is increased hydrostatic pressure leading to increased vascular permeability (Starling Forces) and the clinical implication is increased ventricular stiffness, a leading cause of cardiac failure in transplantation (Circulation 101: 1303-1310, 2000).
• Lifestyle modification and Type 2 diabetes: We demonstrated for the first time that moderate levels of exercise (independent of weight changes) causes increased expression of anti-oxidant enzymes in diabetes, so increasing the bioavailability of nitric oxide, the endogenous vasodilator molecule and platelet anti-coagulant released by the endothelium (Diabetologia 51: 1327-1337; Am J Physiol 295: H1470-H1480; Am J Physiol 296: F700-F708, 2008; Naunyn-Schmiedeberg’s Arch Pharmacol 5: 483-492.). Other findings confirmed that detailed mechanisms of the benefits of exercise in the hearts of aged diabetic mice (Br J Pharmacol 171 (23): 5345-5360;PLoS ONE 8(8): e70248. doi:10.1371/journal.pone.0070248). We have since provided a critical analysis of the challenges facing the creation of exercise pills (to assist those unable to undertake regular physical exercise (Trends Pharmacol Sci. 36(12):906-917).
• Vascular dysregulation in obstructive sleep apnea: Studying obstructive sleep apnea in small laboratory animals is complicated by a number of factors (as we discuss in Lung. 190(2):113-132) and a commonly used approach is to expose rodents to periods of intermittent hypoxia. We show that in this model of sleep apnea, there is endothelial function, likely related to increased oxidative stress (Sleep Med. 15(5):596-602).
• Reference work on free radical biology: “Systems Biology of Free Radicals and Antioxidants”. Handbook of Pharmacology Edited by Ismail Laher. Published by Springer-Verlag. Five volumes and 182 chapters.