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Atherosclerosis I: Introduction01:30

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Atherosclerosis is a progressive disorder characterized by the buildup of plaques on the arterial inner wall, causing them to narrow and harden over time. These plaques comprise lipids, calcium, blood components, carbohydrates, and fibrous tissue. The process primarily affects the intima of large and medium-sized arteries, reducing blood flow in any artery.Etiology and risk factorsThe cause of atherosclerosis is multifactorial, involving a complex interplay among endothelial injury, lipid...
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Immunosenescence accelerates atherosclerosis development in AAV-PCSK9 mouse model.

Jill de Mol1, Virginia Smit1, Mireia N A Bernabé Kleijn1

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Area of Science:

  • Immunology
  • Cardiovascular Science
  • Aging Research

Background:

  • Aging is a primary risk factor for atherosclerotic cardiovascular disease.
  • Immunosenescence, age-related immune system changes, significantly impacts disease progression.
  • Understanding immunosenescence's role in atherosclerosis is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the impact of immunosenescence on atherosclerosis development.
  • To analyze the immune landscape changes in aged mice with induced atherosclerosis.
  • To compare plaque development and immune cell profiles between young and aged mice.

Main Methods:

  • Utilized a recombinant adeno-associated virus encoding PCSK9 (rAAV-PCSK9) in a Western-type diet (WTD) mouse model.
  • Compared atherosclerosis development in young (3-month) and aged (18-month) male C57Bl/6 mice over 10 weeks.
  • Analyzed immune cell populations in peripheral blood, lymphoid organs, and aortic tissue.

Main Results:

  • Aged mice exhibited significantly enhanced atherosclerosis (59% increase) in the aortic root compared to young mice.
  • Aged plaques showed a more advanced phenotype with an increased collagen/macrophage ratio.
  • Aging led to increased leukocytes in the aortic arch, a shift towards effector T cells (Th1, Tregs), and altered B cell populations, alongside elevated antibodies.

Conclusions:

  • Aged mice on a WTD-fed AAV-PCSK9 model display pro-atherogenic immune alterations, including inflammation and senescence, accelerating atherosclerosis.
  • Immunosenescence contributes to increased plaque burden and altered immune responses, driving cardiovascular disease progression.
  • Targeting or reversing age-associated immune changes may offer a novel therapeutic strategy for atherosclerotic cardiovascular disease.