Smooth muscle cells (SMC's) are heterogeneous in their myosin isoform expression. The evidence that this correlates with their contractile function is critical for further understanding their function and dysfunction in normal and pathological states. For example, the vascular disease atherosclerosis is the major cause of morbidity and mortality in humans. It involves a thickening of the intimal layer by, in part, a proliferation of SMC's. Unfortunately, little is know about the myosin isoform expression and mechanical properties of medial SMC's, and virtually nothing is known of the intimal SMC's. We propose investigating the myosin isoform expression and mechanics of single SMCs and SM tissues under normal and experimentally induced pathological conditions. The results will increase our understanding of the biology of the SMC and the molecular basis for the differences in phenotype of the medial and intimal SMCs.
The specific aims of this grant are to test the hypotheses that: 1) SM1/2 MHC tail isoforms but not the SMA/B MHC head or MLC17a/b isoforms correlate with force production. 2) MHC isoforms show differential distribution between and within cells from a given tissue. 3) In contrast to the classical striated muscle length-tension relationship with a unique optimal length (Lo), SMC's can shift (alter) their Lo by varying the organization of contractile units to adapt to different cell lengths. 4) SMC's found in the intimal thickening of an atherosclerotic vessel will differ in their myosin isoform expression and mechanical properties relative to the medial SMC's. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL062237-05A1
Application #
6732287
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Program Officer
Ershow, Abby
Project Start
1999-04-01
Project End
2007-11-30
Budget Start
2003-12-15
Budget End
2004-11-30
Support Year
5
Fiscal Year
2004
Total Cost
$181,250
Indirect Cost
Name
Marquette University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
046929621
City
Milwaukee
State
WI
Country
United States
Zip Code
53201
Eddinger, Thomas J (2014) Smooth muscle-protein translocation and tissue function. Anat Rec (Hoboken) 297:1734-46
Huang, Qian; Babu, Gopal J; Periasamy, Muthu et al. (2013) SMB myosin heavy chain knockout enhances tonic contraction and reduces the rate of force generation in ileum and stomach antrum. Am J Physiol Cell Physiol 304:C194-206
Eddinger, Thomas J (2009) Unique contractile and structural protein expression in dog ileal inner circular smooth muscle. J Smooth Muscle Res 45:217-30
Govindaraju, Sandya R; Bain, James Lw; Eddinger, Thomas J et al. (2008) Vibration causes acute vascular injury in a two-step process: vasoconstriction and vacuole disruption. Anat Rec (Hoboken) 291:999-1006
Eddinger, Thomas J; Meer, Daniel P; Miner, Amy S et al. (2007) Potent inhibition of arterial smooth muscle tonic contractions by the selective myosin II inhibitor, blebbistatin. J Pharmacol Exp Ther 320:865-70
Eddinger, Thomas J; Schiebout, Jessen D; Swartz, Darl R (2007) Adherens junction-associated protein distribution differs in smooth muscle tissue and acutely isolated cells. Am J Physiol Gastrointest Liver Physiol 292:G684-97
Eddinger, Thomas J; Meer, Daniel P (2007) Myosin II isoforms in smooth muscle: heterogeneity and function. Am J Physiol Cell Physiol 293:C493-508
Han, Shaojie; Speich, John E; Eddinger, Thomas J et al. (2006) Evidence for absence of latch-bridge formation in muscular saphenous arteries. Am J Physiol Heart Circ Physiol 291:H138-46
Call, Christopher; Han, Shaojie; Speich, John E et al. (2006) Resistance to pressure-induced dilatation in femoral but not saphenous artery: physiological role of latch? Am J Physiol Heart Circ Physiol 291:H1513-20
Eddinger, Thomas J; Schiebout, Jessen D; Swartz, Darl R (2005) Smooth muscle adherens junctions associated proteins are stable at the cell periphery during relaxation and activation. Am J Physiol Cell Physiol 289:C1379-87

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