Y Chromosome, Hypertension and Cardiovascular Disease: Is Inflammation the Answer?

Shanzana I Khan,Amanda K Sampson,Jaye P F Chin-Dusting,Karen L Andrews,Garry L Jennings

doi:10.3390/ijms20122892

Abstract

It is now becomingly increasingly evident that the functions of the mammalian Y chromosome are not circumscribed to the induction of male sex. While animal studies have shown variations in the Y are strongly accountable for blood pressure (BP), this is yet to be confirmed in humans. We have recently shown modulation of adaptive immunity to be a significant mechanism underpinning Y-chromosome-dependent differences in BP in consomic strains. This is paralleled by studies in man showing Y chromosome haplogroup is a significant predictor for coronary artery disease through influencing pathways of immunity. Furthermore, recent studies in mice and humans have shown that Y chromosome lineage determines susceptibility to autoimmune disease. Here we review the evidence in animals and humans that Y chromosome lineage influences hypertension and cardiovascular disease risk, with a novel focus on pathways of immunity as a significant pathway involved.

Highlights

The male-specific region of the Y chromosome (MSY), which constitutes 95% of its length, does not undergo recombination and is inherited virtually intact from father to son [1]
Given well-established sex differences in adaptive immunity and mounting evidence that Y chromosome haplogroup influences immunity to in turn mediate susceptibility to cardiovascular disease, we investigated whether Y-chromosome-dependent differences in blood pressure (BP) in rodent were associated with Y-chromosome-dependent differences in T cell infiltration [36]
We have provided compelling evidence that Y chromosome lineage predicts T cell infiltration in key cardiovascular organs to in turn influence BP

Summary

Introduction

The male-specific region of the Y chromosome (MSY), which constitutes 95% of its length, does not undergo recombination and is inherited virtually intact from father to son [1]. The essential role of the Y chromosome in male sex determination has overshadowed the possibility that it may exert pleiotropic effects, despite early observations that the main sex determining gene sry is expressed in a number of tissues central to cardiovascular regulation such as the human kidney, the adrenal gland and the brain [2]. Since accumulating evidence in animals and humans suggests Y chromosome lineage may be one of the strongest genetic determinants of coronary artery disease to date [11]. It was found that elevated coronary artery disease risk associated with Y chromosome lineage occurred independently of traditional risk factors but was associated with pathways of immunity. Recent studies in mouse models have shown that Y chromosome lineage is a significant determinant of autoimmunity [12]. We review the evidence from man and rodent supporting a role for the Y in hypertension and cardiovascular disease with a new focus on inflammation and immunity as a significant pathway involved

Y Chromosome and Hypertension

Major Results

Y Chromosome and Vascular Function

Y Chromosome and Inflammation

Conclusions