Overexpression of ABCG1 protein attenuates arteriosclerosis and endothelial dysfunction in atherosclerotic rabbits
The ABCG1 protein is centrally involved in reverse cholesterol transport from the vessel wall. Investigation of the effects of ABCG1 overexpression or knockdown in vivo has produced controversial results and strongly depended on the gene intervention model in which it was studied. Therefore, we investigated the effect of local overexpression of human ABCG1 in a novel model of vessel walldirected adenoviral gene transfer in atherosclerotic rabbits. We conducted local, vascularspecific gene transfer by adenoviral delivery of human ABCG1 (Ad-ABCG1-GFP) in cholesterol- fed atherosclerotic rabbits in vivo. Endothelial overexpression of ABCG1 markedly reduced atheroprogression (plaque size) and almost blunted vascular inflammation, as shown by markedly reduced macrophage and smooth muscle cell invasion into the vascular wall. Also endothelial function, as determined by vascular ultrasound in vivo, was improved in rabbits after gene transfer with Ad-ABCG1- GFP. Therefore, both earlier and later stages of atherosclerosis were improved in this model of somatic gene transfer into the vessel wall. In contrast to results in transgenic mice, overexpression of ABCG1 by somatic gene transfer to the atherosclerotic vessel wall results in a significant improvement of plaque morphology and composition, and of vascular function in vivo.
Adenoviral vector, gene transfer, ABCG1, atherosclerosis.
Martin Ungerer; Corimmun GmbH; Fraunhofer Str. 17; D-82152 Martinsried, Germany. Tel. +49.89.85652010 – Fax: +49.89.85652020 E-email: firstname.lastname@example.org
Share this Article
Related Content In Atherosclerosis
Multimodality Imaging Trials Evaluating the Impact of Omega-3 Fatty Acids on Coronary Artery Plaque Characteristics and Burden
Heart International. 2022;16(1):2–11 DOI: https://doi.org/10.17925/HI.2022.16.1.2
Despite improved treatment of atherosclerotic cardiovascular disease, coronary artery disease (CAD) remains the leading cause of death and disability worldwide.1 Treatment of traditional risk factors, mainly low-density lipoprotein (LDL) cholesterol, is the foundation of atherosclerotic risk reduction. However, a considerable residual risk for cardiovascular disease (CVD) still exists despite reducing LDL cholesterol.2 Beyond traditional risk factors, other […]
Medical Therapy for Secondary Prevention of Atherothrombotic Events in Peripheral Artery Disease
Heart International. 2021;15(1):14-19 DOI: https://doi.org/10.17925/HI.2021.15.1.14
Peripheral artery disease (PAD) is a severe manifestation of systemic atherosclerotic disease that commonly refers to lower-extremity arterial involvement. The global burden of PAD is estimated to involve over 200 million patients, with prevalence increasing by 24% over the past decade.1 In contrast to myocardial infarction and stroke, which are declining in the USA, the […]
The Evolving Role of Omega 3 Fatty Acids in Cardiovascular Disease: Is Icosapent Ethyl the Answer?
Heart International. 2021;15(1):7-13 DOI: https://doi.org/10.17925/HI.2021.15.1.7
There are several beneficial effects of statins on the progression of atherosclerosis, and there have been significant advancements in pharmacotherapies for atherosclerotic cardiovascular disease (ASCVD). However, substantial residual cardiovascular (CV) risk remains, and there is an unmet need to reduce the residual risk of cardiovascular disease (CVD) events.1 There is increased focus on the role […]
Journal articles and more to your inbox
Get the latest clinical insights from touchCARDIOSign me up!