Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

Enhanced postmyocardial infarction fibrosis via stimulation of the transforming growth factor-beta-Smad2 signaling pathway: role of transient receptor potential vanilloid type 1 channels.

Wei Huang; Jack Rubinstein; Alejandro R Prieto; Donna H Wang (Profiled Author: Donna H Wang)

Department of Medicine, B316 Clinical Center, Michigan State University, East Lansing, Michigan, USA.
Journal of hypertension 2010;28(2):367-76.

OBJECTIVE: To test the hypothesis that the transient receptor potential vanilloid type 1 (TRPV1) channels modulate postmyocardial infarction (MI) fibrosis and matrix formation via the transforming growth factor-beta-Smad signaling pathway to conserve cardiac function and geometrical regeneration. BACKGROUND: Several lines of evidence indicate that activation of TRPV1 expressed in afferent nerve fibers innervating the heart may preserve cardiac function after MI. However, the underlying mechanisms of TRPV1-mediated protection are largely unknown. METHODS AND RESULTS: TRPV1-null mutant (TRPV1) and wild-type mice were subjected to left anterior descending coronary ligation or sham operation. Seven days after MI, TRPV1 mice showed an increased infarct size and mortality rate (P < 0.001) when compared with wild-type mice. Enzyme-linked immunosorbent assay analysis showed that transforming growth factor-beta1, vascular endothelial growth factor, and matrix metalloproteinase-2 expression were upregulated to a greater extent in TRPV1 than in wild-type mice after MI (P < 0.001). Western blot showed that Smad2 expression was enhanced in TRPV1 compared with wild-type mice after MI (P < 0.001). Quantitative immunohistochemistry analysis showed that myofibroblast infiltration, capillary density, and collagen content were greater in TRPV1 compared with wild-type mice after MI (P < 0.001), and that the left ventricular lumen was enlarged and the wall thinner in TRPV1 compared with wild-type mice after MI (P < 0.001). Echocardiographic examination showed end-systolic and end-diastolic diameters were increased and the ejection fraction reduced in TRPV1 compared with wild-type mice after MI (P < 0.001). CONCLUSION: Thus, ablation of TRPV1 markedly enhances post-MI fibrosis and impairs myocardial contractile performance, leading to increased propensity of functional heart failure and mortality possibly via stimulation of the transforming growth factor-beta-Smad2 signaling pathway. These data indicate that TRPV1 plays a protective role in MI healing and regeneration.

3 Originating Grant

• 1.

  Wang, Donna H

  Molecular Sensing of Sodium Homeostasis: Anandamide Role

  1 September 2005 - 31 July 2010

  NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

  Total Funding: $ 1,430,055

• 2.

  WANG, DONNA H

  Vanilloid Sensitive Sensory Nerves and Salt Sensitivity

  1 April 2003 - 30 June 2012

  NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

  Total Funding: $ 2,688,280

• 3.

  Wang, Donna H

  Renal Angiotensin II Receptor and Sodium Intake

  14 August 1998 - 29 February 2008

  NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

  Total Funding: $ 1,438,625

Scientific Context

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