Lipoprotein(a): Expanding our knowledge of aortic valve narrowing

Trends Cardiovasc Med. 2021 Jul;31(5):305-311. doi: 10.1016/j.tcm.2020.06.001. Epub 2020 Jun 7.

Abstract

Elevated levels of lipoprotein(a) [Lp(a)] have been identified as an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and, more recently, calcific aortic valve disease (CAVD). CAVD is a slow, progressive disorder presenting as severe trileaflet calcification known as aortic valve stenosis (AS) that impairs valve motion and restricts ventricular outflow. AS afflicts 2% of the aging population (≥ 65 years) and tends to be quite advanced by the time it presents clinical symptoms of exertional angina, syncope, or heart failure. Currently, the only effective clinical therapy for AS patients is surgical or transcatheter aortic valve replacement. Evidence is accumulating that Lp(a) can exacerbate pathophysiological processes in CAVD, specifically, endothelial dysfunction, formation of foam cells, and promotion of a pro-inflammatory state. In the valve milieu, the pro-inflammatory effects of Lp(a) are manifested in valve thickening and mineralization through pro-osteogenic signaling and changes in gene expression in valve interstitial cells that is primarily facilitated by the oxidized phospholipid content of Lp(a). In AS pathogenesis, an incomplete understanding of the role of Lp(a) at the molecular level and the absence of appropriate animal models are barriers for the development of specific and effective clinical interventions designed to mitigate the role of Lp(a) in AS. However, the advent of effective therapies that dramatically lower Lp(a) provides the possibility of the first medical treatment to halt AS progression.

Keywords: Aortic stenosis; Calcific aortic valve disease; Lipoprotein(a); Oxidized phospholipids.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aged
  • Animals
  • Aortic Valve / drug effects
  • Aortic Valve / metabolism*
  • Aortic Valve / pathology*
  • Aortic Valve Stenosis / diagnosis
  • Aortic Valve Stenosis / drug therapy
  • Aortic Valve Stenosis / genetics
  • Aortic Valve Stenosis / metabolism*
  • Calcinosis / diagnosis
  • Calcinosis / drug therapy
  • Calcinosis / genetics
  • Calcinosis / metabolism*
  • Disease Models, Animal
  • Female
  • Foam Cells / metabolism
  • Foam Cells / pathology
  • Humans
  • Hypolipidemic Agents / therapeutic use
  • Lipoprotein(a) / genetics
  • Lipoprotein(a) / metabolism*
  • Male
  • Oligonucleotides / therapeutic use
  • Oxidation-Reduction
  • Phospholipids / metabolism

Substances

  • AKCEA-APO(a)-LRx
  • Hypolipidemic Agents
  • LPA protein, human
  • Lipoprotein(a)
  • Oligonucleotides
  • Phospholipids

Supplementary concepts

  • Aortic Valve, Calcification of