Targeting Vascular Fibrosis

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Background The world health organization has recently identified hypertension as the number 1 risk factor for premature death in the world. As well, the population in many countries is rapidly aging leading to an increasing prevalence of hypertension. Isolated systolic hypertension is the most common form of hypertension in the elderly. It is associated with substantial mortality and morbidity. Although many anti-hypertensives exist, these treatments often fail to regulate the systolic blood pressure without lowering the diastolic pressure making treatment of isolated systolic hypertension difficult. Technology Overview Vascular stiffening with age and the deposition of collagen in the blood vessel wall is an important determinant of hypertension. The increased workload of the heart in this circumstance, due to aortic stiffening, results in left ventricular hypertrophy and chronic heart disease. Researchers at McMaster University target this vascular fibrosis induced by hypertension in the blood vessel wall to reverse the underlying pathology that drives blood pressure higher with aging. The researchers have a unique molecular target, Inositol- requiring enzyme 1 (IRE1)/X-box binding protein 1 spliced (XBP1s) mediated protein synthesis, lead compounds, and established assay systems in vitro and in vivo to assess the ability of novel compounds to inhibit the target.