ISH-PL-3: MY ROAD TO ACADEMIC CARDIOLOGY

Abstract

My road to academic cardiology started on our dairy farm in upstate New York, where I learned the pleasures and responsibilities of work at very young age. We were given a little lamb by a neighbor and I was given major responsibility as a young child for caring for him. The work ethic extended to schooling. I studied hard and completed undergraduate studies at Cornell and medical school at Columbia, then began medical residency at Columbia's teaching hospital. There my career was interrupted when the residency class ahead of me filled up with Vietnam veterans. That bad luck turned out to be the best of fortunes when I was introduced to Edgar Haber, then Chief of the Cardiac Unit at the Massachusetts General Hospital. Ed was an innovative scientist, a great mentor and a great leader in cardiovascular medicine. He spurred my interest for the first time in biomedical research and laboratory medicine. Under his guidance, I completed studies that showed for the first time that conversion of the inactive decapeptide angiotensin I to the pressor octapeptide angiotensin II occurred in the pulmonary circulation, not the systemic circulation or in plasma. Another simple study demonstrated the critical role of renin release in maintaining blood pressure when a person assumed the upright posture. The study showed that the renin angiotensin system functions abnormally in people with upright posture-induced vasovagal syncope. I also developed a burning interest in heart disease in women, specifically, on whether postmenopausal women should use hormone replacement therapy to prevent cardiovascular disease. At that time, women were recommended not to use estrogen replacement therapy for cardiovascular disease prevention because previous studies, carried out in older post-menopausal women, showed no benefit from estrogen. I hypothesized that the integrity of estrogen receptors and the vasoprotective effects of estrogen disappear with aging and tested the hypothesis that favorable responses to estrogen treatment are lost in injured arteries of aging animals (rats). I found that aged ovariectomized rats lost the vasoprotective and anti-inflammatory responses to exogenous estrogen that were seen in younger animals. These results may explain the lack of estrogen responsive in vasoprotection in the vasculature of elderly post-menopausal women treated with hormones. More recently, findings from my studies in isolated cells and animal models have led to the design and conduct of a variety of clinical studies of hypertension and its treatment in human subjects, including, most recently, pregnant women.