Aortic stenosis

Cardiology section

Coronary artery disease (CAD) is a common heart condition and a leading global cause of death. It occurs when arteries supplying blood to the heart narrow due to cholesterol and plaque buildup, known as atherosclerosis. Reduced blood flow can deprive the heart

muscle of oxygen, leading to complications. Aortic stenosis, another heart condition, typically develops later in life, often due to calcium deposits narrowing the heart valve. However, congenital factors and chest radiation can also contribute to its occurrence.

ABOUT AORTIC STENOSIS

UNDERSTANDING aortic stenosis

Understanding Aortic Stenosis: Causes, Prevalence, and Risk Factors

Rheumatic fever is another potential cause, typically arising after strep throat or scarlet fever. However, valve issues may not manifest until 5 to 10 years after rheumatic fever occurrence.

Rheumatic fever has become less common in the United States. Aortic stenosis affects around 2% of individuals over 65 years old, with a higher prevalence in men compared to women.

Aortic stenosis (AS) is primarily a degenerative condition associated with aging and calcification of the aortic valve. However, there are also genetic factors that can predispose individuals to develop AS. Here are some of the key genes associated with aortic stenosis:

NOTCH1

Mutations in the NOTCH1 gene have been identified in individuals with congenital aortic valve anomalies, including bicuspid aortic valve (BAV), which is a common predisposing factor for AS. NOTCH1 is involved in valve development and homeostasis, and mutations in this gene can disrupt valve formation and function, leading to valvular abnormalities and potential stenosis later in life.

GATA5

Mutations in the GATA5 gene have also been associated with BAV and congenital heart defects, including aortic valve anomalies. GATA5 is a transcription factor involved in heart development, and mutations in this gene can disrupt normal valve morphogenesis, predisposing individuals to AS.

LRP5

Mutations in the LRP5 gene have been implicated in aortic valve calcification and stenosis. LRP5 is involved in bone metabolism and the Wnt signaling pathway, which plays a role in osteoblast differentiation and bone formation. Dysregulation of LRP5 signaling may contribute to abnormal bone formation and calcification of the aortic valve.

APOB

Variants in the APOB gene have been associated with calcific aortic valve disease (CAVD), a common cause of AS in older adults. APOB encodes apolipoprotein B, a protein involved in lipid metabolism and the formation of lipoprotein particles. Dyslipidemia and abnormal lipid deposition in the aortic valve may promote inflammation and calcification, leading to valve stenosis.

ACTA2

Mutations in the ACTA2 gene have been implicated in familial thoracic aortic aneurysms and dissections (FTAAD), which can sometimes be associated with aortic valve abnormalities, including stenosis. ACTA2 encodes smooth muscle alpha-2 actin, a protein involved in smooth muscle cell contraction and vascular integrity. Dysfunctional smooth muscle cells in the aortic valve may contribute to valve degeneration and stenosis.

TGFBR2

Mutations in the TGFBR2 gene have been identified in individuals with Loeys-Dietz syndrome, a connective tissue disorder characterized by arterial aneurysms and valve abnormalities, including aortic stenosis. TGFBR2 is involved in the transforming growth factor-beta (TGF-β) signaling pathway, which regulates cell growth, differentiation, and extracellular matrix homeostasis. Dysregulation of TGF-β signaling may contribute to valve degeneration and stenosis.

These genes play various roles in valve development, homeostasis, and calcification, and mutations in these genes can predispose individuals to develop aortic stenosis.

However, the genetic basis of aortic stenosis is complex and likely involves interactions between multiple genetic and environmental factors. Further research is needed to elucidate the underlying mechanisms and identify potential therapeutic targets for AS.