Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Nov 18:6:335.
doi: 10.3389/fphys.2015.00335. eCollection 2015.

"Smooth Muscle Cell Stiffness Syndrome"-Revisiting the Structural Basis of Arterial Stiffness

Nancy L Sehgel  1 , Stephen F Vatner  2 , Gerald A Meininger  3
Affiliations
Review

"Smooth Muscle Cell Stiffness Syndrome"-Revisiting the Structural Basis of Arterial Stiffness

Nancy L Sehgel et al. Front Physiol. .

Abstract

In recent decades, the pervasiveness of increased arterial stiffness in patients with cardiovascular disease has become increasingly apparent. Though, this phenomenon has been well documented in humans and animal models of disease for well over a century, there has been surprisingly limited development in a deeper mechanistic understanding of arterial stiffness. Much of the historical literature has focused on changes in extracellular matrix proteins-collagen and elastin. However, extracellular matrix changes alone appear insufficient to consistently account for observed changes in vascular stiffness, which we observed in our studies of aortic stiffness in aging monkeys. This led us to examine novel mechanisms operating at the level of the vascular smooth muscle cell (VSMC)-that include increased cell stiffness and adhesion to extracellular matrix-which that may be interrelated with other mechanisms contributing to arterial stiffness. We introduce these observations as a new concept-the Smooth Muscle Cell Stiffness Syndrome (SMCSS)-within the field of arterial stiffness and posit that stiffening of vascular cells impairs vascular function and may contribute stiffening to the vasculature with aging and cardiovascular disease. Importantly, this review article revisits the structural basis of arterial stiffness in light of these novel findings. Such classification of SMCSS and its contextualization into our current understanding of vascular mechanics may be useful in the development of strategic therapeutics to directly target arterial stiffness.

Keywords: aorta; atomic force microscopy; cell biology; cell stiffness; collagen; cytoskeleton; elastin; vascular smooth muscle cells.

PubMed Disclaimer

Figures

Figure 1
Figure 1
(A) Aortic stiffness increased in old males and females compared to younger monkeys. However, aortic stiffness was increased more in old males than old females. (B) There was little significant difference in collagen density in those groups. (C) Elastin density was decreased more in old males than the females. (D) The collagen/elastin ratio increased more in old males than old females. Reprinted from Qiu et al. (2007). *P < 0.05 vs. corresponding young animals; †P < 0.05 vs. corresponding old male monkeys.
Figure 2
Figure 2
Mechanical properties of single VSMC measured by AFM. (A) Distribution of force as a function of indentation in young (pink) (n = 40 cells) and old (blue) (n = 76 cells) monkeys. Increased cell stiffness is evident as higher force requirement for indentation. (B) VSMC stiffness 4 fold increased in old vs. young monkeys. *P < 0.05 vs. young monkeys. Reprinted from Qiu et al. (2010).
Figure 3
Figure 3
Hypertension in spontaneously hypertensive rats (SHR) vs. Wistar-Kyoto (WKY) rats (A) was associated with increased aortic stiffness, measured by pulse wave velocity (B) and stiffness was also increased in individual vascular smooth muscle cells (VSMCs), as determined by atomic force microscopy measurements (C). *P < 0.05, compared to WKY. Reprinted from Sehgel et al. (2013).
Figure 4
Figure 4
Contact mode height image (top) for a typical old and young monkey aortic VSMC. The height image data was pseudo- colored and slightly tilted to enhance relief contrast. The images reveal an extensive network of actin filaments in the old monkey VSMC compared to the Young monkey reflecting extensive cytoskeletal changes. Color bars index the cell height. Scale is given at the bottom. Reprinted from Zhu et al. (2012).
Figure 5
Figure 5
Example of a 30 min records of cell elastic moduli for an old (A) and young (B) monkey VSMC. Blue line shows raw data and the red line displays the reconstructed data after analysis. Data were processed using an eigendecomposition partition to permit the amplitude, frequency and phase components of the oscillation to be separated on cell-by-cell basis. Averaged data for old VSMC (n = 24) and young (n = 27) show differences in dynamic oscillatory behavior of old and young VSMC (C). Reprinted from Zhu et al. (2012).
Figure 6
Figure 6
Increases arterial stiffness develops from both extracellular (ECM) and cellular mechanisms.
Figure 7
Figure 7
Smooth muscle stiffness syndrome (SMCSS) is characteristic of increased arterial stiffness. SMCSS describes the aberrant increased cortical stiffness and adhesion to fibronectin (FN) observed in vascular smooth muscle cells derived from stiff vessels. SMCSS may be an important therapeutic target for direct modulation of arterial stiffness.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. AlGhatrif M., Strait J. B., Morrell C. H., Canepa M., Wright J., Elango P., et al. . (2013). Longitudinal trajectories of arterial stiffness and the role of blood pressure: the Baltimore longitudinal study of aging. Hypertension 62, 934–941. 10.1161/HYPERTENSIONAHA.113.01445 - DOI - PMC - PubMed
    1. Anderson T. J. (2006). Arterial stiffness or endothelial dysfunction as a surrogate marker of vascular risk. Can. J. Cardiol. 22(Suppl. B), 72B–80B. 10.1016/S0828-282X(06)70990-4 - DOI - PMC - PubMed
    1. Armentano R. L., Levenson J., Barra J. G., Fischer E. I., Breitbart G. J., Pichel R. H., et al. . (1991). Assessment of elastin and collagen contribution to aortic elasticity in conscious dogs. Am. J. Physiol. 260(6 Pt 2), H1870–H1877. - PubMed
    1. Avolio A. P., Clyde K. M., Beard T. C., Cooke H. M., Ho K. K., O'Rourke M. F. (1986). Improved arterial distensibility in normotensive subjects on a low salt diet. Arteriosclerosis 6, 166–169. 10.1161/01.ATV.6.2.166 - DOI - PubMed
    1. Avolio A. P., Deng F. Q., Li W. Q., Luo Y. F., Huang Z. D., Xing L. F., et al. . (1985). Effects of aging on arterial distensibility in populations with high and low prevalence of hypertension: comparison between urban and rural communities in China. Circulation 71, 202–210. 10.1161/01.CIR.71.2.202 - DOI - PubMed

LinkOut - more resources