Molecular, cellular and vascular biology of hypertension

Hypertension, high blood pressure (BP), and its consequences contribute significantly to worldwide morbidity and mortality. Hypertension is the major cause of stroke, kidney disease and cardiac failure in Scotland, and it is predicted that by 2025 the number of adults with hypertension will increase by 60%. This is attributed, in part, to the growing problem of associated risk factors including obesity and diabetes. Despite its widespread prevalence and intense research into its pathophysiology and etiology, only 5% of patients with hypertension have an identifiable cause. Hypertension is the product of dynamic interactions between genetic, physiological and environmental factors. Most patients with high BP have “essential hypertension”, the cause of which remains unknown.

Pathophysiological processes associated with hypertension include endothelial dysfunction and alterations in vascular function and structure (vascular remodelling), which impact on cardiac, cerebral and renal function. At the cellular level vascular cells undergo proliferation, migration, contraction and inflammation. At the molecular level, abnormal signal transduction contributes to these cellular alterations. My research focuses on such signaling pathways in the vascular system. Specific areas of research include 1) NADPH oxidases, oxidative stress and redox signaling; 2) vascular biology of angiotensin II and aldosterone; 3) TRPM6/7 and ion transport in the vasculature and 4) tyrosine kinases, inflammation and vascular remodeling. These studies are conducted at the molecular, cellular, tissue, whole animal and clinical levels and have a strong translational focus.

The overall objective of my research program is to investigate the subcellular and cellular processes that underlie vascular changes, such that specific mechanisms may be identified to further the understanding of vascular pathobiology of hypertension and to discover new therapeutic targets in the prevention and management of hypertension and associated cardiovascular disease.