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Inflammatory and metabolic mechanisms underlying the calcific aortic valve disease

      Highlights

      • There are currently no medical interventions capable of delaying or halting progression of calcific aortic stenosis.
      • Calcific aortic valve disease (CAVD) is an active process that involves mechanical and biochemical factors.
      • This review will focus on the role of inflammation and metabolic risk factors.
      • This provides the future therapeutic strategies for the CAVD progression.

      Abstract

      Although calcific aortic stenosis is a very common disease with major adverse cardiovascular events and healthcare costs, there are no effective medical interventions to delay or halt its progression. Cardiometabolic risk factors, including smoking and male sex, are linked to aortic stenosis. Emerging studies have identified important regulatory roles for immunological and inflammatory responses, including oxidized lipids, various cytokines, and biomineralization. Recent clinical and experimental studies in atherosclerosis and osteoporosis have demonstrated that oxidative stress and oxidized lipids decrease bone formation in the skeletal system while they increase bone formation in the cardiovascular system. Multidisciplinary factors contribute to vascular calcification, including inflammation and metabolic regulation of osteogenesis in the cardiovascular system via similar signaling pathways as bone formation.
      Calcific aortic valve disease (CAVD) is no longer considered a simple passive process of calcium deposition that occurs with advanced age. Biomineralization in CAVD is a complex, regulated process that involves valvular, circulating, bone marrow–derived cells, macrophage heterogeneity and genetic factors along with biochemical and mechanical factors. The current review will discuss the recently discovered important role of inflammation, metabolic risk factors, and molecular and cellular mechanisms that promote CAVD, as well as the link between osteogenic signals in the skeletal and cardiovascular systems. This may inform future therapeutic strategies for CAVD progression.

      Keywords

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