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Andreas Edsfeltdt

Andreas Edsfeldt

Associate professor

Andreas Edsfeltdt

Evidence for a protective role of placental growth factor in cardiovascular disease

Author

  • Yihong Chen
  • Anna Hultgårdh Nilsson
  • Isabel Goncalves
  • Andreas Edsfeldt
  • Gunnar Engström
  • Olle Melander
  • Marju Orho-Melander
  • Uwe Rauch
  • Christoffer Tengryd
  • Shreenidhi M. Venuraju
  • Avijit Lahiri
  • Chun Liang
  • Jan Nilsson

Summary, in English

Placental growth factor (PlGF) is a mitogen for endothelial cells, but it can also act as a proinflammatory cytokine. Because it promotes early stages of plaque formation in experimental models of atherosclerosis and was implicated in epidemiological associations with risk of cardiovascular disease (CVD), PlGF has been attributed a pro-atherogenic role. Here, we investigated whether PlGF has a protective role in CVD and whether elevated PlGF reflects activation of repair processes in response to vascular stress. In a population cohort of 4742 individuals with 20 years of follow-up, high baseline plasma PlGF was associated with increased risk of cardiovascular death, myocardial infarction, and stroke, but these associations were lost or weakened when adjusting for cardiovascular risk factors known to cause vascular stress. Exposure of cultured endothelial cells to high glucose, oxidized low-density lipoprotein (LDL) or an inducer of apoptosis enhanced the release of PlGF. Smooth muscle cells and endothelial cells treated with PlGF small interference RNA demonstrated that autocrine PlGF stimulation plays an important role in vascular repair responses. High expression of PlGF in human carotid plaques removed at surgery was associated with a more stable plaque phenotype and a lower risk of future cardiovascular events. When adjusting associations of PlGF with cardiovascular risk in the population cohort for plasma soluble tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-2, a biomarker of cellular stress, a high PlGF/TRAIL receptor-2 ratio was associated with a lower risk. Our findings provide evidence for a protective role of PlGF in CVD.

Department/s

  • Vessel Wall Biology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Cardiovascular Research - Translational Studies
  • Cardiovascular Research - Epidemiology
  • EpiHealth: Epidemiology for Health
  • Cardiovascular Research - Hypertension
  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Immunity and Atherosclerosis

Publishing year

2020

Language

English

Publication/Series

Science Translational Medicine

Volume

12

Issue

572

Document type

Journal article

Publisher

American Association for the Advancement of Science (AAAS)

Topic

  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Vessel Wall Biology
  • Cardiovascular Research - Translational Studies
  • Cardiovascular Research - Epidemiology
  • Cardiovascular Research - Hypertension
  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Immunity and Atherosclerosis

ISBN/ISSN/Other

  • ISSN: 1946-6242