Medial arterial calcification in ageing and disease: current evidence and knowledge gaps

Area of Science:

• Cardiovascular Medicine
• Vascular Biology
• Biogerontology

Background:

• Medial arterial calcification (MAC) is a hallmark of arterial aging, often silent but a critical risk factor for cardiovascular events, limb ischemia, and amputation in susceptible individuals, particularly those with diabetes mellitus and chronic kidney disease.
• MAC pathogenesis involves vascular smooth muscle cell phenotype switching, leading to hydroxyapatite deposition, medial layer destruction, and intimal thickening.
• Shared signaling pathways in aging and disease contribute to MAC, fundamentally altering hemodynamics through arterial stiffening and intimal thickening.

Purpose of the Study:

• To highlight the critical role of medial arterial calcification (MAC) as a risk factor for cardiovascular morbidity and mortality.
• To emphasize the lack of comprehensive understanding regarding MAC's impact on hemodynamics.
• To underscore the need for further research into MAC's molecular pathogenesis and hemodynamic consequences for early detection, prevention, and treatment.

Main Methods:

• Review of existing literature on medial arterial calcification (MAC) pathogenesis, clinical implications, and hemodynamic effects.
• Analysis of the biological features of MAC, including vascular smooth muscle cell phenotype switching and hydroxyapatite deposition.
• Discussion of current diagnostic limitations (ankle-brachial index, ultrasound, X-ray) for detecting early-stage MAC.

Main Results:

• Medial arterial calcification (MAC) is a significant contributor to arterial aging and a critical risk factor for cardiovascular disease and limb-threatening ischemia.
• MAC causes arterial stiffening and intimal thickening, leading to significant, yet incompletely understood, hemodynamic alterations.
• Current clinical detection methods are limited to advanced stages of MAC, highlighting a gap in early diagnosis.

Conclusions:

• Medial arterial calcification (MAC) presents numerous opportunities for early detection, prevention, and intervention due to its slow progression.
• The absence of effective pharmacological treatments necessitates further research into MAC's molecular mechanisms and hemodynamic impact.
• Developing strategies to prevent, reverse, or delay MAC is crucial, as revascularization remains the primary treatment for symptomatic patients.