Abca1 Deficiency Protects the Heart Against Myocardial Infarction-Induced Injury Interview with:

Dr. Mieke Louwe (1) and 
Prof. dr. Miranda van Eck (2)
1Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
2Leiden Academic Centre for Drug Research, Leiden University, Leiden,
The Netherlands


Dr. Mieke Louwe


Prof. Miranda van-Eck What is the background for this study?

Response: ATP-binding cassette transporter A1 (Abca1) is a key protein facilitating the production of high-density lipoprotein (HDL) and the maintenance of macrophage cholesterol homeostasis. Patients and mice with mutations in the Abca1 gene have virtually no HDL in their circulation. Since HDL plays a key protective role in atherosclerosis, by exerting several cardioprotective functions, up regulation of Abca1 is considered as an important novel therapeutic strategy to prevent atherosclerotic cardiovascular disease. Although the role of Abca1 in atherosclerosis is extensively studied, the interplay between Abca1 and myocardial infarction, an acute cardiovascular event often resulting from rupture of advanced atherosclerotic plaques, has not yet been investigated. What are the main findings?

Response: We provide the first evidence that, despite the protective role of Abca1 in atherosclerosis, Abca1 exerts detrimental effects on myocardial infarction-induced cardiac injury.

In order to study the importance of Abca1 after myocardial infarction we performed permanent coronary artery ligation experiments in whole-body Abca1 deficient mice and wild type controls. Abca1 deficient mice developed surprisingly smaller myocardial infarction sizes 1 day and 14 days post-myocardial infarction.

Unaltered infarct size was observed upon ex vivo myocardial infarction induction in isolated hearts from Abca1 deficient mice and wild type mice, indicating that Abca1 deficiency in cardiomyocytes did not contribute to the observed effect.
We noticed that the reduced infarct sizes in Abca1 deficient mice were accompanied by an increase in circulating leukocytes. Therefore, we also studied the importance of Abca1 deficiency in hematopoietic cells. Control wild type mice transplanted with Abca1 deficient bone marrow showed a clear trend towards a reduced myocardial infarction size. Altogether, this suggests a detrimental role for Abca1 in hematopoietic cells after myocardial infarction. What should readers take away from your report?

Response: Our study shows that hematopoietic Abca1 has unanticipated, unfavorable effects on cardiac injury following myocardial infarction. What recommendations do you have for future research as a result of this study?

Response: Future treatment strategies aiming at ameliorating ABCA1 function to reduce atherosclerosis should be pursued with care, given the potential adverse effects of ABCA1 on cardiac remodeling following myocardial infarction. Is there anything else that you would like to add?

Response: We would like to thank the Netherlands CardioVascular
Research Initiative: the Dutch Heart Foundation, Dutch Federation
of University Medical Centers, the Netherlands Organisation for
Health Research and Development, and the Royal Netherlands
Academy of Sciences for funding this research via the GENIUS project ‘Generating the best evidence-based pharmaceutical targets for atherosclerosis’ (CVON2011). Thank you for your contribution to the community.

Citation: Louwe et al. Abca1 deficiency protects the heart against myocardial infarction-induced injury. Atherosclerosis. 2016 Jun 11;251:159-163.

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on July 7, 2016 by Marie Benz MD FAAD