Testosterone deficiency promotes arterial stiffening independent of sex chromosome complement

Area of Science:

• Cardiovascular Science
• Endocrinology
• Genetics

Background:

• Sex hormones and chromosomes are critical in cardiovascular disease.
• Low testosterone is linked to cardiovascular and cardiometabolic issues like inflammation, atherosclerosis, and type 2 diabetes.
• Testosterone replacement is generally safe or beneficial for male cardiovascular health.

Purpose of the Study:

• To investigate the roles of sex hormones and sex chromosome complement in arterial stiffening.
• To understand the inherent contribution of sex chromosomes (XX and XY) and testosterone in vascular health.

Main Methods:

• Utilized four core genotype male mice.
• Mice were either intact or castrated at eight weeks, followed by an eight-week hormone clearance period.
• Assessed blood pressure, pulse wave velocity, echocardiography, and ex vivo passive vascular mechanics.

Main Results:

• Arterial stiffening, but not blood pressure, was more pronounced in castrated mice, irrespective of sex chromosome complement.
• Castration led to changes in stress-strain curves and carotid wall thinning.
• The XX sex chromosome complement, without testosterone, resulted in increased aortic collagen deposition and Kdm6a gene expression.

Conclusions:

• Testosterone deprivation exacerbates arterial stiffening and vascular wall remodeling.
• Castration in XX male mice leads to increased collagen type 1 alpha 1 (Col1α1) expression.
• Castrated XX mice exhibited reduced aortic contractile gene expression compared to castrated XY mice.