Short communication: vascular smooth muscle cell stiffness as a mechanism for increased aortic stiffness with aging

Circ Res. 2010 Sep 3;107(5):615-9. doi: 10.1161/CIRCRESAHA.110.221846. Epub 2010 Jul 15.

Abstract

Rationale: Increased aortic stiffness, an important feature of many vascular diseases, eg, aging, hypertension, atherosclerosis, and aortic aneurysms, is assumed because of changes in extracellular matrix (ECM).

Objective: We tested the hypothesis that the mechanisms also involve intrinsic stiffening of vascular smooth muscle cells (VSMCs).

Methods and results: Stiffness was measured in vitro both by atomic force microscopy (AFM) and in a reconstituted tissue model, using VSMCs from aorta of young versus old male monkeys (Macaca fascicularis) (n=7/group), where aortic stiffness increases by 200% in vivo. The apparent elastic modulus was increased (P<0.05) in old (41.7+/-0.5 kPa) versus young (12.8+/-0.3 kPa) VSMCs but not after disassembly of the actin cytoskeleton with cytochalasin D. Stiffness of the VSMCs in the reconstituted tissue model was also higher (P<0.05) in old (23.3+/-3.0 kPa) than in young (13.7+/-2.4 kPa).

Conclusions: These data support the novel concept, not appreciated previously, that increased vascular stiffness with aging is attributable not only to changes in ECM but also to intrinsic changes in VSMCs.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / metabolism
  • Age Factors
  • Aging / metabolism
  • Aging / pathology*
  • Animals
  • Aorta, Thoracic / pathology
  • Aortic Diseases / etiology
  • Aortic Diseases / pathology*
  • Cells, Cultured
  • Cytochalasin D / pharmacology
  • Cytoskeleton / drug effects
  • Cytoskeleton / metabolism
  • Elastic Modulus
  • Integrin beta1 / metabolism
  • Macaca fascicularis
  • Male
  • Microscopy, Atomic Force
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology*
  • Tubulin / metabolism
  • Vimentin / metabolism

Substances

  • Actins
  • Integrin beta1
  • Tubulin
  • Vimentin
  • Cytochalasin D