Abstract
The physiologic role of smooth muscle structure in defining arterial function is poorly understood. We aimed to elucidate the relationship between vascular smooth muscle architecture and functional contractile output. Using microcontact printing and muscular thin film technology, we engineered in vitro vascular tissues with strictly defined geometries and tested their contractile function. In all tissues, vascular smooth muscle cells (VSMCs) were highly aligned with in vivo-like spindle architecture, and contracted physiologically in response to stimulation with endothelin-1. However, tissues wherein the VSMCs were forced into exaggerated spindle elongation exerted significantly greater contraction force per unit cross-sectional area than those with smaller aspect ratios. Moreover, this increased contraction did not occur in conjunction with an increase in traditionally measured contractile phenotype markers. These results suggest that cellular architecture within vascular tissues plays a significant role in conferring tissue function and that, in some systems, traditional phenotype characterization is not sufficient to define a functionally contractile population of VSMCs.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives
-
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
-
Actin Cytoskeleton / metabolism
-
Cell Nucleus / physiology
-
Cell Shape / physiology*
-
Cells, Cultured
-
Cytoskeletal Proteins / metabolism
-
Dimethylpolysiloxanes / chemistry
-
Dose-Response Relationship, Drug
-
Endothelin-1 / pharmacology
-
Fibronectins / pharmacology
-
Humans
-
Laminin / pharmacology
-
Muscle Contraction / drug effects
-
Muscle Contraction / physiology*
-
Muscle Proteins / metabolism
-
Muscle, Smooth, Vascular / cytology*
-
Muscle, Smooth, Vascular / drug effects
-
Muscle, Smooth, Vascular / physiology*
-
Myocytes, Smooth Muscle / cytology*
-
Myocytes, Smooth Muscle / drug effects
-
Myocytes, Smooth Muscle / metabolism
-
Myosin Heavy Chains / metabolism
-
Smooth Muscle Myosins / metabolism
-
Tissue Engineering / methods
-
Tissue Scaffolds / chemistry
-
Umbilical Veins / cytology
-
rho-Associated Kinases / antagonists & inhibitors
Substances
-
Cytoskeletal Proteins
-
Dimethylpolysiloxanes
-
Endothelin-1
-
Fibronectins
-
Laminin
-
Muscle Proteins
-
SMTN protein, human
-
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
-
rho-Associated Kinases
-
Smooth Muscle Myosins
-
Myosin Heavy Chains
-
fasudil