Immune Mechanisms of Heart Valve Development, Homeostasis, and Disease

Valvular heart disease is among the most common cardiovascular conditions, usually presenting as aortic stenosis or mitral regurgitation. Clinically significant structural and functional anomalies can arise through congenital malformation, genetic variants, cardiovascular dysfunction, infectious disease sequelae, or chronic inflammation that can progress over time, necessitating surgical replacement or repair. The most common types of valve disease requiring surgical intervention are mitral valve prolapse, often with myxomatous changes due to congenital malformation or infectious disease, and aortic valve stenosis resulting from calcific aortic valve disease. Recent studies have identified critical contributions of immune cells to aortic and mitral valve pathophysiology. Moreover, preclinical studies demonstrate valve disease mechanisms related to innate or adaptive immune cell infiltration that could be targeted in human valvular heart disease using existing or emerging anti-inflammatory approaches. Here, we review recent findings of immune cell contributions and molecular mechanisms of myxomatous valve disease, rheumatic heart disease, and calcific aortic valve disease with potential therapeutic applications.