Extracellular matrix and pulmonary hypertension

Control of vascular smooth muscle cell contractility

Kyung-Mi Lee, Kenneth Y. Tsai, Ning Wang, Donald E. Ingber

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Pulmonary hypertension is characterized by increased vascular resistance due to smooth muscle cell hyperactivity and excess deposition of extracellular matrix (ECM) in the vessel wall. We investigated the possibility that changes in cell-ECM interactions may play an active role in this process by modifying the contractile response of pulmonary vascular smooth muscle (PVSM) cells. Contractility was measured within individual cultured PVSM cells, when resting or stimulated with vasoactive agents, by quantitating changes in stiffness of the cytoskeleton (CSK) using magnetic twisting cytometry (N. Wang, J. P. Butler, and D. E. Ingber. Science 260: 1124-1127, 1993). Control studies confirmed that changes in CSK stiffness closely paralleled alterations in cell contraction and relaxation as measured in response to endothelin-1 (ET-1) and dibutyryl guanosine 3′,5′-cyclic monophosphate (cGMP), respectively, in a collagen gel contraction assay. CSK stiffness and contractile tone in cultured PVSM cells increased in direct proportion as the density of fibronectin (FN) coating was raised from 10 to 500 ng/well in 96-well plates. Dibutyryl cGMP had no effect in cells on low FN, although it completely inhibited the FN-dependent increase in CSK stiffness on higher ECM densities. In contrast, ET-1 induced the greatest increase in CSK stiffness on the intermediate FN density (100 ng/well). The reduced sensitivity to ET-1 on high FN was not due to dysfunction of the contractile apparatus nor to changes in protein tyrosine phosphorylation. Taken together, these results show that ECM can modulate PVSM cell contractility and suggest that the changes in ECM observed in hypertensive vessels could play an important role in the etiology of this disease.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume43
Issue number1
Publication statusPublished - 1998 Jan 1
Externally publishedYes

Fingerprint

Cytoskeleton
Vascular Smooth Muscle
Fibronectins
Pulmonary Hypertension
Smooth Muscle Myocytes
Extracellular Matrix
Endothelin-1
Lung
Guanosine
Vascular Resistance
Tyrosine
Collagen
Gels
Phosphorylation
Proteins

Keywords

  • Cell mechanics
  • Cytoskeleton
  • Fibronectin
  • Gel contraction
  • Magnetic twisting cytometry

ASJC Scopus subject areas

  • Physiology

Cite this

Extracellular matrix and pulmonary hypertension : Control of vascular smooth muscle cell contractility. / Lee, Kyung-Mi; Tsai, Kenneth Y.; Wang, Ning; Ingber, Donald E.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 43, No. 1, 01.01.1998.

Research output: Contribution to journalArticle

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