Sex, Endothelial Cell Functions, and Peripheral Artery Disease

Siân P Cartland; Christopher P Stanley; Christina Bursill; Freda Passam; Gemma A Figtree; Sanjay Patel; Jacky Loa; Jonathan Golledge; David A Robinson; Sarah J Aitken; Mary M Kavurma

doi:10.3390/ijms242417439

Sex, Endothelial Cell Functions, and Peripheral Artery Disease

Int J Mol Sci. 2023 Dec 13;24(24):17439. doi: 10.3390/ijms242417439.

Authors

Siân P Cartland¹, Christopher P Stanley¹, Christina Bursill^{2

3}, Freda Passam⁴, Gemma A Figtree^{4

5}, Sanjay Patel^{1

6}, Jacky Loa⁶, Jonathan Golledge^{7

8}, David A Robinson⁶, Sarah J Aitken^{4

9}, Mary M Kavurma¹

Affiliations

¹ Heart Research Institute, The University of Sydney, Sydney, NSW 2042, Australia.
² South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia.
³ Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia.
⁴ Faculty of Health and Medicine, The University of Sydney, Sydney, NSW 2050, Australia.
⁵ Kolling Institute of Medical Research, Sydney, NSW 2064, Australia.
⁶ Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia.
⁷ Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia.
⁸ Department of Vascular and Endovascular Surgery, The Townsville University Hospital, Townsville, QLD 4814, Australia.
⁹ Concord Institute of Academic Surgery, Concord Repatriation General Hospital, Sydney, NSW 2139, Australia.

Abstract

Peripheral artery disease (PAD) is caused by blocked arteries due to atherosclerosis and/or thrombosis which reduce blood flow to the lower limbs. It results in major morbidity, including ischemic limb, claudication, and amputation, with patients also suffering a heightened risk of heart attack, stroke, and death. Recent studies suggest women have a higher prevalence of PAD than men, and with worse outcomes after intervention. In addition to a potential unconscious bias faced by women with PAD in the health system, with underdiagnosis, and lower rates of guideline-based therapy, fundamental biological differences between men and women may be important. In this review, we highlight sexual dimorphisms in endothelial cell functions and how they may impact PAD pathophysiology in women. Understanding sex-specific mechanisms in PAD is essential for the development of new therapies and personalized care for patients with PAD.

Keywords: endothelial cell dysfunction; peripheral artery disease; sex differences.

Publication types

Review

MeSH terms

Atherosclerosis*
Endothelial Cells
Female
Humans
Intermittent Claudication
Lower Extremity / blood supply
Male
Peripheral Arterial Disease* / therapy
Risk Factors

Grants and funding

M.M.K. and S.P.C. are supported by grants from the National Health and Medical Research Council (NHMRC APP1188218). J.G. is supported by grants from the NHMRC, MRFF Queensland Government, and Heart Foundation. S.J.A. is supported by grants from the MRFF, Vascular Foundation, and Heart Foundation.