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Primary Mouse Aortic Smooth Muscle Cells Exhibit Region- and Sex-Dependent Biological Responses In Vitro.

Niyousha Karbasion1, Yujun Xu1,2, J Caleb Snider1,2

  • 1Department of Mechanical Engineering & Materials Science, Washington University at St. Louis, St. Louis, MO 63130.

Journal of Biomechanical Engineering
|February 29, 2024
PubMed
Summary

Vascular smooth muscle cells (VSMCs) from different mouse aorta regions show distinct sex-based behaviors. Thoracic VSMCs exhibit sex-dependent responses to growth factors and proliferation, impacting cardiovascular disease (CVD) research.

Keywords:
abdominalaortacontractilitymechanobiologyproliferationsex differencessmooth musclethoracic

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Area of Science:

  • Cardiovascular Biology
  • Mechanobiology
  • Vascular Cell Biology

Background:

  • Cardiovascular disease (CVD) is a leading global cause of death, with notable sex-based disparities in prevalence and mortality.
  • Understanding regional and sex-specific differences in cardiovascular cell behavior is crucial for elucidating CVD initiation and progression.
  • Primary vascular smooth muscle cells (VSMCs) play a key role in vascular function and remodeling.

Purpose of the Study:

  • To characterize in vitro region- and sex-dependent behaviors of primary aortic VSMCs from male and female mice.
  • To investigate differences in VSMC contractility and proliferation under basal and stimulated conditions.

Main Methods:

  • Primary VSMCs were isolated from the thoracic and abdominal aorta of male and female mice.
  • Cell contractility was assessed using traction force microscopy (TFM) and collagen gel contraction assays.
  • Cell proliferation was measured using a colorimetric metabolic assay (MTT).
  • Responses were evaluated with and without stimulation by transforming growth factor-beta 1 (TGF-β1).

Main Results:

  • Gene expression and TFM revealed region- and sex-dependent VSMC behaviors.
  • Collagen gel contraction was consistent across sexes and aortic regions under baseline conditions.
  • Thoracic VSMCs demonstrated sex-dependent sensitivity to TGF-β1-induced contraction (female > male) and proliferation (female > male).
  • These sex-dependent responses were not observed in abdominal VSMCs.

Conclusions:

  • Primary VSMCs possess intrinsic region- and sex-dependent biological responses relevant to cardiovascular disease (CVD) presentation.
  • These findings highlight the importance of considering sex and aortic region in CVD research.
  • Future studies should incorporate factors like inflammation and sex hormones to further explore in vitro mechanobiological responses in CVD.