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Robert C. Tarazi, MD Ahsan Husain, PhD, FAHA Freddy Abi-Samra, MD Fetnat Fouad-Tarazi, MB, BCH, MD for pioneering hypertension research, Dr. Page was the first to identify hyperten- sion not as a single isolated disease but as a "mosaic" dependent upon a complexity of individual and intermixing mechanisms involving the biochemical and nervous systems and other factors, such as struc- tural changes in arteries and organs. His research also helped shape the understand- ing and treatment of hypertension and heart attack by uncovering the link between high blood pressure and heart disease. In addition, Dr. Page isolated the peptide angiotensin, a key player in hyper- tension, and was among the first to recognize high blood pressure as a disease that could be treated. It was Dr. Page's leadership that estab- lished the structure of Cleveland Clinic's highly effective Cardiovascular Research within the Research Division. While the overall focus was hypertension, researchers worked in different areas such as cell biol- ogy, biochemistry, immunology, physiology, clinical science, etc., collaborating as necessary to unravel pressing questions. By the time Dr. Fouad-Tarazi joined Cleveland Clinic's Research Division, clinical cardiologists were grappling with a new puzzle. They turned to their cardio- vascular research colleagues to help determine why some patients tended to develop acute hypertension on the heels of coronar y arter y by pass surger y. Pinpointing the reason for this spike — and a method to counteract it — became the first research priority for Dr. Fouad-Tarazi at Cleveland Clinic. "We found that doing a stellate gan- glion block on one side caused the blood pressure to go down and stay down," she says. "So we made the link between the sympathetic nervous system and the development of hypertension via neurogenic reflexes originating from the coronary vessels." Clinical and experimental research at Cleveland Clinic and in other centers had revealed that the sympathetic ner- vous system, along with stress-induced hormones called catecholamines, is an important "regulator" of hypertension. Other regulators of hypertension identi- fied through pivotal translational research at Cleveland Clinic include: + The role of the renin angiotensin aldosterone system + The role of blood volume and other hemodynamic factors + The role of salt intake, salt sensitivity, the kidneys and the adrenal glands. Cardiovascular research, however, was not limited to the identification of factors acting on the heart and body to cause hypertension. It also included the effects that hypertension can have on the heart in terms of both structure (i.e., left ventricular hypertrophy) and function (i.e., diastolic dysfunction). In essence, the work of the Clinic's translational researchers helped unveil and charac- terize the bidirectional relationship between blood pressure and the heart. Hypertrophy and Heart Failure Cleveland Clinic's groundbreaking collaborative research in cardiac hyper- trophy also began with a question on the clinical side, and played a major role in changing the perspective about left ventricular hypertrophy in hyperten- sion from "protective" to "harbinger" of the seeds of heart failure, among other factors. This led Dr. R. C. Tarazi and others to explore the possibility and the outcome of regression of left ventricular hypertrophy in hypertension. Moreover, although hypertension is typically associated with enlargement of the wall of the heart (hypertrophy), physicians were noticing a lack of cor- relation between heart size and blood pressure in some cases, suggesting that blood pressure was not the only factor in hypertrophy. The key turned out to be myotrophin, a protein discovered by researchers in Cleveland Clinic's Department of Molecular Cardiology. Myotrophin is encoded by the MTPN gene that controls cardiac mass. Similarly, clinicians knew that the angiotensin-converting-enzyme (ACE) inhibitor captopril could be used to keep congestive heart failure in check for long periods of time. Dr. Fouad-Tarazi and her colleagues — including molecular biologist Ahsan Husain, PhD, FAHA, now a Professor of Cardiology at Emory University — wanted to know why. "I ca me to Clevela nd Clin ic in 1979 because it was already a mecca for research on the renin angiotensin PHOTO COURTESY OF CLEVELAND CLINIC PHOTO © JOE SMITHBERGER, NORTH CANTON PHOTO COURTESY OF DR. AHSAN HUSAIN PHOTO COURTESY OF OCHSNER HEALTH SYSTEM 2 0 1 5 S E P T E M B E R /O C T O B E R ■ M D N E W S . CO M ■ MD NEWS Cleveland/Akron/Canton | 9