University of Tennessee Health Science Center Campus Photos
OWA WebMail  /  SiteMap  /  Contact Information
Home
Chief's Message
Clinical
Educational
Faculty
Fellowship
Fellows' Page
News & Events
Patients
Research
Web Links

Research

Overview

The major focus of the Division of Cardiovascular Diseases is in the pathogenesis and management of heart failure, a major health problem of ever increasing proportions particularly amongst the elderly and African-Americans.  Basic and applied studies in heart failure are featured.  Each are funded from federal and nonfederal sources.

Basic Science

One major theme of cellular and molecular science-based studies conducted in the Division's experimental laboratories (Coleman Building) centers on the regulation of tissue architecture and cellular composition, termed structural remodeling.  It focuses primarily on turnover of the extracellular matrix, the heart's fibrillar collagen matrix, and myofibroblasts, phenotypically transformed fibroblasts integral to fibrous tissue formation.  Our findings have challenged long-held dogma that infarct scar is dead tissue.  Instead, we now know that the infarct scar is a dynamic tissue with resident, metabolically-active myofibroblasts nourished by a neovasculature.  Where they come from and what we should do about them are ongoing questions.

A second major theme addresses the integrative physiology that accompanies aldosteronism in rats.  This includes:  pathophysiologic responses leading to the induction of oxidative stress; an immunostimulatory state involving circulating lymphocytes and monocytes; and a wasting of bone.  An interdisciplinary team of basic and applied scientists working together in a culture of cooperation and common purpose to unravel the mysteries responsible for the appearance of the systemic illness that accompanies aldosteronism, an integral feature of the complex neurohormonal profile found in human CHF.

Clinical Science

Clinical investigations, conducted at the Regional Medical Center, the VAMC, and the Methodist University Hospital, broadly focus on the origins and management of chronic heart failure.  Several areas of interest are highlighted here.  First, the cellular origins and management of cytokine imbalance that contributes to generalized wasting, termed cardiac cachexia, and which includes a loss of bone mineral density as well as lean body and fat mass.  Cells responsible for the cytokine "storm" seen in heart failure have not been identified.  Challenging current wisdom and the heart's role in their production, we have targeted cells of the monocyte-phagocyte system for investigation.  Novel management strategies have been targeted to interrupt proinflammatory cytokine production and reverse wasting.  Second, the relationship between heart failure (whether mild or severe), plasma cytokines, and reduced bone mineral density.  Third, our search for a "physiologic diuretic" to overcome avid sodium retention that characterizes advanced heart failure and which would prove useful in its home management.  This includes specific projects that address the utility of the following to enhance sodium excretion: timed recumbency, with and without loop diuretic; head-out water immersion; enhanced external counterpulsation; and a program of intermittent phosphodiesterase inhibitor treatment.  Each project is based on promoting more favorable relationships between effector hormones of the renin-angiotensin-aldosterone system and the heart's family of natriuretic peptides.

Below is a listing of recent publications in basic and applied research in heart failure.

  1. Sun Y, Zhang J, Lu L, Chen SS, Quinn MT, Weber KT. Aldosterone-induced inflammation in the rat heart. Role of oxidative stress. Am J Pathol 2002;161:1773-1781.
  2. Gerling IC, Sun Y, Ahokas RA, Wodi LA, Bhattacharya SK, Warrington KJ, Postlethwaite AE, Weber KT. Aldosteronism: an immunostimulatory state precedes the proinflammatory/fibrogenic cardiac phenotype. Am J Physiol Heart Circ Physiol 2003;285:H813-H821.
  3. Ahokas RA, Warrington KJ, Gerling IC, Sun Y, Wodi LA, Herring PA, Lu L, Bhattacharya SK, Postlethwaite AE, Weber KT. Aldosteronism and peripheral blood mononuclear cell activation. A neuroendocrine-immune interface. Circ Res 2003;93:e124-e135.
  4. Weber KT, Gerling IC, Kiani MF, Guntaka RV, Sun Y, Ahokas RA, Postlethwaite AE, Warrington KJ. Aldosteronism in heart failure: a proinflammatory/fibrogenic cardiac phenotype. Search for biomarkers and potential drug targets. Curr Drug Targets 2003;4:505-516.
  5. Weber KT. Aldosteronism revisited. Perspectives on less well-recognized actions of aldosterone. J Lab Clin Med 2003;142:71-82.
  6. Weber KT, Sun Y, Wodi LA, Munir A, Jahangir E, Ahokas RA, Gerling IC, Postlethwaite AE, Warrington KJ. Toward a broader understanding of aldosterone in congestive heart failure. J Renin Angiotensin Aldosterone Syst 2003;4:155-163.
  7. Chhokar VS, Sun Y, Bhattacharya SK, Ahokas RA, Myers LK, Xing Z, Smith RA, Gerling IC, Weber KT. Loss of bone minerals and strength in rats with aldosteronism. Am J Physiol Heart Circ Physiol 2004;287:H2023-H2026.
  8. Sun Y, Zhang J, Lu L, Bedigian MP, Robinson AD, Weber KT. Tissue angiotensin II in the regulation of inflammatory and fibrogenic components of repair in the rat heart. J Lab Clin Med 2004;143:41-51.
  9. Weber KT. From inflammation to fibrosis: a stiff stretch of highway. Hypertension 2004;43:716-719.
  10. Weber KT. Furosemide in the long-term management of heart failure. The good, the bad and the uncertain. J Am Coll Cardiol 2004;44:1308-1310.
  11. Weber KT. The neuroendocrine-immune interface gone awry in aldosteronism. Cardiovasc Res 2004;64:381-383.
  12. Ahokas RA, Sun Y, Bhattacharya SK, Gerling IC, Weber KT. Aldosteronism and a proinflammatory vascular phenotype. Role of Mg2+, Ca2+ and H2O2 in peripheral blood mononuclear cells. Circulation 2005;111:51-57.
  13. Chhokar VS, Sun Y, Bhattacharya SK, Ahokas RA, Myers LK, Xing Z, Smith RA, Gerling IC, Weber KT. Hyperparathyroidism and the calcium paradox of aldosteronism. Circulation 2005;111:871-878.
  14. Runyan AL, Chhokar VS, Sun Y, Bhattacharya SK, Runyan JW, Weber KT. Bone loss in rats with aldosteronism. Am J Med Sci 2005;330:1-7.
  15. Law PH, Sun Y, Bhattacharya SK, Chhokar VS, Weber KT. Diuretics and bone loss in rats with aldosteronism. J Am Coll Cardiol 2005;46:142-146.
  16. Runyan AL, Sun Y, Bhattacharya SK, Ahokas RA, Chhokar VS, Gerling IC, Weber KT. Responses in extracellular and intracellular calcium and magnesium in aldosteronism. J Lab Clin Med 2005;146:76-84.
  17. Vidal A, Sun Y, Bhattacharya SK, Ahokas RA, Gerling IC, Weber KT. The calcium paradox of aldosteronism and the role of the parathyroid glands. Am J Physiol Heart Circ Physiol 2006;290:H286–H294.
  18. Khouzam RN, Dishmon DA, Farah V, Flax SD, Carbone LD, Weber KT. Secondary hyperparathyroidism in patients with untreated and treated congestive heart failure. Am J Med Sci 2006;331:30-34.

Copyright ©2008 The University of Tennessee Health Science Center · Memphis, Tennessee 38163 · Telephone 901-448-5500