Increased mesenchymal podoplanin expression is associated with calcification in aortic valves

Area of Science:

• Cardiovascular Biology
• Cellular Biology
• Biochemistry

Background:

• Calcific aortic valve disease (CAVD) progresses from valvular sclerosis to severe aortic stenosis (AS).
• Mesenchymal cells differentiating into osteoblasts are implicated in aortic valve calcification.
• Podoplanin, a glycoprotein, is found in lymphatic vessels, osteoblasts, and atherosclerotic lesions.

Purpose of the Study:

• To investigate podoplanin expression in human aortic valves across different disease stages.
• To determine the association of podoplanin with calcification and cellular phenotypes in CAVD.

Main Methods:

• Immunohistochemistry and quantitative real-time PCR (RT-PCR) were used to assess podoplanin expression.
• Human aortic valve samples from control, aortic regurgitation (AR), AR with fibrosis (AR+f), and AS groups were analyzed.

Main Results:

• Podoplanin expression was significantly elevated in AR+f and AS groups compared to control and AR groups.
• Podoplanin levels correlated positively with the extent of calcification and vascularity.
• Podoplanin was detected in osteoblasts, osteocytes, chondrocytes, macrophages, and myofibroblast-like cells, not just lymphatic endothelium.

Conclusions:

• Increased podoplanin expression characterizes CAVD and is linked to valvular interstitial cell differentiation.
• Podoplanin is associated with myofibroblast-like cells producing calcium in CAVD.
• Tricuspid valves exhibit higher calcification-associated podoplanin levels than bi/unicuspid valves.