Hypertension

Mailing Address:
700 Albany Street, W508
Boston, MA 02118
Phone: (617) 638-4025
Fax: (617) 638-4027

Sections

Click here to view and download the 2009 Hypertension Annual Report

Research Activities
The Hypertension and Atherosclerosis Section has always been heavily research oriented. Its faculty members continue to pursue several lines of ongoing research that have been funded mainly by grants from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI).

The Hypertension research program at The Boston University Medical Center (BUMC) was one of five SpecializedCenters of Research (SCORs) funded by the NIH between 1975 and 2006 and the only one to obtain continuous funding over this 30-year period. Clinical and experimental studies conducted over this period helped elucidate the role of the renin-angiotensin system in hypertension and heart failure and pioneered the use of angiotensin-converting enzyme inhibition or angiotensin receptor blockade in the treatment of these conditions. In this respect, the Section continued the BUMC tradition that was established in the 1950’s with the introduction of the first oral treatments for hypertension using rauwolfa derivatives and thiazide diuretics.

The Section’s faculty members collaborate with faculty from other BUMC departments and the Framingham Heart Study, as well as scientists from The Jackson Laboratory in Bar Harbor, Maine.

The Section has also participated in the NIH-funded Program of Genomic Applications, via a subcontract with the Jackson Laboratory (Principal Investigator Luanne Peters, PhD).

Independent R01 grants have provided the funds for most research projects.  Included are:  a project that investigates the role of alpha2-adrenergic receptors in hypertension, using genetically engineered mice with deleted genes or transgenes with added genes for receptor subtypes, as well as antisense technology for gene treatment in rats; another project researches the role of bradykinin in preventing ischemic heart disease using various bradykinin analogs and studying interactions with various autacoids. Other ongoing-research projects include the role of the novel Cmya3 gene (identified and sequenced by the Section’s researchers) in ischemic cardiomyopathy and the non-enzymatic cellular effects of the angiotensin-converting enzyme.

Clinical Activities
Senior Section faculty are recognized nationally and internationally for their contributions to the pathophysiology and treatment of hypertension and its complications. The Section conducts three weekly clinical sessions at the East Newton Campus, where outpatients referred by physicians from other BUMC departments or from the community are evaluated. These are highly selected patients with resistant hypertension who need evaluation for underlying pathology or who have complicated management problems with multiple coexisting conditions. A clinical faculty member is also available for inpatient consultations at all times, as well as for telephone consultations with other BUMC physicians, the Boston community, and out-of-state- medical professionals

Education
In the current year, there are two research fellows, both on scholarships from overseas.  Post-doctoral fellows and graduate students are given the opportunity to master research skills and carry out their own projects, present their data in national meetings, and publish in peer-reviewed journals.

The Section offers also elective rotations to fourth-year medical students or interns who follow one of the senior faculty members during outpatient clinical sessions and inpatient consultations. The senior Section faculty are also involved in numerous other educational activities, including seminars, teaching rounds, courses in cardiovascular pharmacology to medical students, as well as lectures to physicians, other health professionals, or the lay public (e.g., the “Mini Medical School”).

Major Accomplishments
Haralambos Gavras, M.D., is Chief of the Section of Hypertension, and Professor of Medicine. Dr. Gavras is nationally and internationally recognized for his work on the renin-angiotensin system. He was the first to introduce angiotensin receptor blockade and angiotensin-converting enzyme (ACE) inhibition in the treatment of patients with hypertension and/or heart failure. He has received numerous distinctions and awards, including his election as Chairman of the Council of High Blood Pressure Research of the American Heart Association 1996-1998, President of the American Society of Hypertension 2002-2004 and the 2004 “Franz Volhard Award” of the World Heart Federation. Irene Gavras, M.D., Professor of Medicine, has participated in numerous clinical trials and experimental studies, and has served as officer in various committees of the American Heart Association and the American Society of Hypertension.  Hector Lucero, PhD, is a Research Assistant Professor of Medicine and a 1989-1990 recipient of Fellowship from the National Biotechnology Program of Argentina.  Ekaterina Kintsurashvili, PhD, is a Research Assistant Professor of Medicine, who won the American Society of Hypertension’s Young Investigator’s Award for 2002.  Athanasios J. Manolis, MD, Adjunct Assistant Professor of Medicine is past president of the Mediterranean Association of Cardiology and Cardiac Surgery and current secretary of the European Society of Hypertension. He actively participates in the Section’s clinical research as well as in multi-center, multi-national clinical trials. Drs. H. Gavras and I. Gavras have participated in regular 4-year Study Sections of the NIH in the past and ad hoc Study Sections or Advisory Committees of various NIH Programs in recent years.

Athanasios J. Manolis, MD, Adjunct Assistant Professor of Medicine is past president of the Mediterranean Association of Cardiology and Cardiac Surgery and current secretary of the European Society of Hypertension. He actively participates in the Section’s clinical research as well as in multi-center, multi-national clinical trials.

Drs. H. Gavras and I. Gavras have participated in regular 4-year Study Sections of the NIH in the past and ad hoc Study Sections or Advisory Committees of various NIH Programs in recent years.

Recent Publications

Ignjacev-Lazich I, Kintsurashvili E, Johns C, Vitseva O, Duka A, Shenouda S, Gavras I, Gavras H: Angiotensin-converting enzyme regulates bradykinin receptor gene expression. Am J Physiol Heart Circ Physiol 289:H1814-1820, 2005.  PMID:  16219810

Duka A, Schwartz F, Duka I, Johns C, Melista E, Gavras I, Gavras H.  A novel Gene (Cmya3) induced in the heart by angiotensin II dependent but not salt dependent hypertension in mice. Am J Hypertens 19: 275-281, 2006. PMID: 16500513

Duka A, Duka I, Gao G, Shenouda S, Gavras I, Gavras H: Role of bradykinin B1 and B2 receptors in normal blood pressure regulation. Am J Physiol Endocrinol Metab 291:E268-274, 2006.

Yang D, Zhang Y, Nguyen HG, Koupenova M, Chauhan AK, Makitalo M, Jones MR, St Hilaire C, Seldin DC, Toselli P, Lamperti E, Schreiber BM, Gavras H, Wagner DD, Ravid K: The A2B adenosine receptor protects against inflammation and excessive vascular adhesion. J Clin Invest 116:1913-1923, 2006. PMID: 16823489

Shenouda SM, Johns C, Gavras I, Gavras H: Long-Term Inhibition of the Central alpha(2B)-Adrenergic Receptor Gene Via Recombinant AAV-Delivered Antisense in Hypertensive Rats. Am J Hypertens 19:1135-1143, 2006. PMID: 17070424

Cardoso de Carvalho F, Bregagnollo E, Santos Silva V, Brunie A, da Silva Franco RJ, Martin LC, Gavras I, Gavras H:  Frequency of coronary artery disease in patients with renal artery stenosis without clinical manifestations of coronary insufficiency. Am J Hypertens 19:1125-1128, 2006.

Sun B, Kintsurashvili E, Ona D, Ignjacev-Lazich I, Gavras I, Gavras H: Inhibition of the alpha(1D)-adrenergic receptor gene by RNA interference (RNAi) in rat vascular smooth muscle cells and its effects on other adrenergic receptors. Vascul Pharmacol 46:367-372, 2007. PMID: 17307398

Duka A, Kintsurashvili E, Duka I, Ona D, Hopkins TA, Bader M, Gavras I, Gavras H: Angiotensin-converting enzyme inhibition after experimental myocardial infarct: role of the kinin B1 and B2 receptors. Hypertension 51:1352-1357, 2008. PMID: 18347228

Silva VS, Martin LC, Franco RJ, Carvalho FC, Bregagnollo EA, Castro JH, Gavras I, Gavras H: Pleiotropic Effects of Statins May Improve Outcomes in Atherosclerotic Renovascular Disease.  Am J Hypertens 21:1163-1168, 2008.

Kintsurashvili E, Shenouda S, Ona D, Ona L, Ahmad S, Ravid K, Gavras I, Gavras H: Hypertension in transgenic mice with brain-selective overexpression of the alpha2B-adrenoceptor. Am J Hypertens 22:41-45, 2009. PMID: 18989257

Gavras, H.  Pathogenesis of Hypertension:  A Review.  J  Med Sci 2:25-28, 2009.

Lucero HA, Kintsurashvili E, Marketou ME, Gavras H: Cell signaling, internalization and nuclear localization of the angiotensin converting enzyme in smooth muscle cells and endothelial cells. J Biol Chem 285:5555-5568, 2010. PMID:20022959

McCalmon SA, Desjardins DM, Ahmad S, Davidoff KS, Snyder CM, Sato K, Ohashi K, Kielbasa OM, Mathew M, Ewen EP, Walsh K, Gavras H, Naya FJ: Modulation of Angiotensin II-Mediated Cardiac Remodeling by the MEF2A Target Gene Xirp2. Circ Res 106: 952-960, 2010.PMID: 20093629

Marketou M, Kintsurashvili E,  Papanicolaou KN, Lucero HA, Gavras I,  Gavras H Cardioprotective effects of a selective b2 receptor agonist of bradykinin post acute myocardial infarct.  Am J Hypertens 23:562-568, 2010. PMID: 20186129

Manolis AJ, Marketou ME, Gavras I, Gavras H: Cardioprotective properties of bradykinin: role of the B(2) receptor. Hypertens Res 33:772-777, 2010. PMID: 20093629