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Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
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Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation

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HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype

Rajeev Malhotra1,2, Andreas C Mauer3, Christian L Lino Cardenas3,4

  • 1Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. rmalhotra@mgh.harvard.edu.

Nature Genetics
|October 30, 2019
PubMed

Insights

Researchers identified genetic links to abdominal aortic calcification, discovering HDAC9 as a key factor. This finding offers new insights into vascular calcification and cardiovascular event prediction.

Area of Science:

  • Genetics
  • Cardiovascular Science
  • Vascular Biology

Background:

  • Aortic calcification is a significant predictor of cardiovascular events.
  • Understanding the genetic basis of aortic calcification is crucial for risk assessment.

Purpose of the Study:

  • To identify single nucleotide polymorphisms (SNPs) associated with abdominal aortic calcification (AAC) and descending thoracic aortic calcification (DTAC).
  • To investigate the role of identified genes in vascular calcification.

Main Methods:

  • Genome-wide association meta-analysis of AAC (n=9,417) and DTAC (n=8,422).
  • In vitro studies using human aortic smooth muscle cells to assess HDAC9 expression and function.
  • In vivo studies using matrix Gla protein-deficient mice lacking HDAC9.

Main Results:

  • Two genetic loci, HDAC9 and RAP1GAP, were significantly associated with AAC.
  • No SNPs reached genome-wide significance for DTAC.
  • Increased HDAC9 expression promoted calcification and reduced contractility in human aortic smooth muscle cells.
  • HDAC9 inhibition reversed these effects.
  • Mice lacking HDAC9 showed a 40% reduction in aortic calcification and improved survival.

Conclusions:

  • This study identifies HDAC9 as the first genetic risk locus for abdominal aortic calcification.
  • HDAC9 plays a novel role in the development of vascular calcification.
  • Findings provide a translational link between genetics and vascular calcification, impacting cardiovascular event prediction.

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