Tissue-specific roles of ABCA1 influence susceptibility to atherosclerosis

Liam R Brunham1, Roshni R Singaraja, MyNgan Duong

  • 1Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.

Insights

ATP-binding cassette transporter A1 (ABCA1) influences atherosclerosis. Hepatic ABCA1 expression protects against atherosclerosis, while macrophage ABCA1 deletion shows no significant effect on disease progression.

Area of Science:

  • Cardiovascular Biology
  • Lipid Metabolism
  • Atherosclerosis Research

Background:

  • ATP-binding cassette transporter, subfamily A, member 1 (ABCA1) is crucial for HDL cholesterol metabolism.
  • The precise role of ABCA1 in atherosclerosis susceptibility remains debated.

Purpose of the Study:

  • To investigate the role of ABCA1 in atherosclerosis using genetic models.
  • To determine the specific contributions of ABCA1 in different tissues to atherogenesis.

Main Methods:

  • Utilized transgenic overexpression of human ABCA1 in Ldlr(-/-) mice.
  • Employed tissue-specific Abca1 inactivation in Apoe(-/-) and Ldlr(-/-) mouse models.
  • Assessed atherosclerosis development and HDL cholesterol levels.

Main Results:

  • ABCA1 overexpression reduced atherosclerosis in Ldlr(-/-) mice.
  • Hepatic Abca1 deficiency in Apoe(-/-) mice led to lower HDL cholesterol and accelerated atherosclerosis.
  • Macrophage-specific Abca1 deletion in Ldlr(-/-) mice did not alter atherosclerotic lesion area.

Conclusions:

  • Physiological ABCA1 expression modulates atherosclerosis susceptibility.
  • Hepatic ABCA1 is a key site for atheroprotection.
  • Selective deletion of macrophage ABCA1 does not significantly impact atherogenesis.
Abstract

Related Concept Videos

Atherosclerosis I: Introduction01:30

Atherosclerosis I: Introduction

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...
Coronary Artery Disease I: Introduction01:30

Coronary Artery Disease I: Introduction

Coronary Artery Disease (CAD): An Overview with Scientific InsightsCoronary Artery Disease (CAD), often referred to as C-A-D, is a prevalent blood vessel disorder classified under the broader category of atherosclerosis. Atherosclerosis is a pathological process characterized by the hardening and narrowing of arteries due to the accumulation of atherosclerotic plaques. These plaques are composed of cholesterol, fatty substances, inflammatory cells, calcium, and fibrin, reducing blood flow to...
Atherosclerosis III: Management01:26

Atherosclerosis III: Management

Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
Coronary Artery Disease II: Pathophysiology01:26

Coronary Artery Disease II: Pathophysiology

Coronary Artery Disease (CAD) originates from a series of events that impair the function of coronary arteries, the blood vessels responsible for delivering oxygen-rich blood to the heart muscle. The pathophysiology of CAD is closely linked to atherosclerosis, a chronic inflammatory and lipid-driven condition affecting the vascular endothelium.1. Endothelial DamageThe process begins with damage to the vascular endothelium, which serves as a protective barrier between the blood and the vessel...
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
ABC Transporters: Exporter01:31

ABC Transporters: Exporter

ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...