ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017
Cholesterol-Lowering Gene Therapy Counteracts the Development of Non-ischemic Cardiomyopathy in Mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- Gene- and cell-based therapy in cardiovascular diseases.Journal of cardiovascular pharmacology · 2025Article
- Current Understanding on the Role of Lipids in Macrophages and Associated Diseases.International journal of molecular sciences · 2022Review
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- Apolipoprotein E4 Is Associated with Right Ventricular Dysfunction in Dilated Cardiomyopathy-An Animal and In-Human Comparative Study.International journal of molecular sciences · 2021Article
- Protective Effects of Estrogen on Cardiovascular Disease Mediated by Oxidative Stress.Oxidative medicine and cellular longevity · 2021Review
- High-Density Lipoprotein-Targeted Therapies for Heart Failure.Biomedicines · 2020Review
- Nox2 Upregulation and p38α MAPK Activation in Right Ventricular Hypertrophy of Rats Exposed to Long-Term Chronic Intermittent Hypobaric Hypoxia.International journal of molecular sciences · 2020Article
- Article
- Cholesterol-Lowering Gene Therapy Prevents Heart Failure with Preserved Ejection Fraction in Obese Type 2 Diabetic Mice.International journal of molecular sciences · 2019Article
- Effective Treatment of Diabetic Cardiomyopathy and Heart Failure with Reconstituted HDL (Milano) in Mice.International journal of molecular sciences · 2019Article
- Successful treatment of established heart failure in mice with recombinant HDL (Milano).British journal of pharmacology · 2018Article
- Reconstituted HDL (Milano) Treatment Efficaciously Reverses Heart Failure with Preserved Ejection Fraction in Mice.International journal of molecular sciences · 2018Article
- Targeting Cholesterol in Non-ischemic Heart Failure: A Role for LDLR Gene Therapy?Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A causal role of hypercholesterolemia in non-ischemic heart failure has never been demonstrated. Adeno-associated viral serotype 8 (AAV8)-low-density lipoprotein receptor (AAV8-LDLr) gene transfer was performed in LDLr-deficient mice without and with pressure overload induced by transverse aortic constriction (TAC). AAV8-LDLr gene therapy resulted in an 82.8% (p < 0.0001) reduction of plasma cholesterol compared with controls. Mortality rate was lower (p < 0.05) in AAV8-LDLr TAC mice compared with control TAC mice (hazard ratio for mortality 0.457, 95% confidence interval [CI] 0.237-0.882) during 8 weeks of follow-up. AAV8-LDLr gene therapy attenuated cardiac hypertrophy, reduced interstitial and perivascular fibrosis, and decreased lung congestion in TAC mice. Cardiac function, quantified by invasive hemodynamic measurements and magnetic resonance imaging, was significantly improved 8 weeks after sham operation or after TAC in AAV8-LDLr mice compared with respective control groups. Myocardial protein levels of mammalian target of rapamycin and of acetyl-coenzyme A carboxylase were strikingly decreased following cholesterol lowering in mice without and with pressure overload. AAV8-LDLr therapy potently reduced cardiac glucose uptake and counteracted metabolic remodeling following pressure overload. Furthermore, oxidative stress and myocardial apoptosis were decreased following AAV8-LDLr therapy in mice with pressure overload. In conclusion, cholesterol-lowering gene therapy potently counteracts structural and metabolic remodeling, and enhances cardiac function.
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