The objective of this proposal is to test the hypothesis that activation of specific PKC isoform(s) is a major step in a signal transduction cascade leading to maintained contraction of coronary smooth muscle.
The specific aims are: 1) to identify the Ca2+-dependent and Ca2+-independent isoforms of PKC expressed in coronary smooth muscle; 2) to determine the subcellular distribution of PKC isoforms in resting and activated coronary smooth muscle cells; 3) to determine the physiological intracellular Ca2+ requirement for activation and translocation of PKC isoforms in situ; 4) to determine whether activation of specific PKC isoforms(s) and contraction of coronary smooth muscle have a cause-and-effect relationship; and 5) to determine whether specific PKC isoforms are overly expressed or hyperactive in coronary smooth muscle of animal models of coronary vasospasm. These studies aim to provide an understanding of the cellular mechanisms underlying coronary smooth muscle contraction and a possible pathophysiological basis of coronary vasospasm.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
7R29HL052696-06
Application #
6674458
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Program Officer
Liang, Isabella Y
Project Start
1997-06-01
Project End
2004-05-31
Budget Start
2002-11-01
Budget End
2004-05-31
Support Year
6
Fiscal Year
2001
Total Cost
$117,838
Indirect Cost
Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115