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Immune Dysregulation in Myocardial Fibrosis, Steatosis, and Heart Failure: Current Insights from HIV and the General Population

  • HIV Pathogenesis and Treatment (AL Landay and NS Utay, Section Editors)
  • Published:
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Abstract

Purpose of Review

HIV is an independent risk factor for heart

failure (HF). Cardiac imaging studies in people with HIV (PWH) have identified myocardial pathologies, namely fibrosis and steatosis, that likely contribute to the higher risk of HF. In this review, we survey existing epidemiological, clinical, and mechanistic literature to identify potential pathways that may contribute to the burden of myocardial fibrosis and steatosis among PWH.

Recent Findings

Multiple cohort studies over the past 20 years have demonstrated a roughly 2-fold higher risk of incident HF in PWH, as well as a disproportionate burden of myocardial fibrosis and steatosis in PWH without HF. Both myocardial fibrosis and steatosis are known contributors to HF in adults without HIV. Pathways involving the NLRP3 inflammasome, TGF-β1, and adipocyte dysfunction are known to play a crucial role in the development of myocardial fibrosis and steatosis. Upregulation of these pathways in HIV due to direct effects of viral proteins, persistent immune dysregulation, gut epithelial breakdown and dysbiosis, and toxicities from antiretroviral therapy may contribute to myocardial dysfunction in HIV. Understanding these pathways may lead to more precise diagnostic and therapeutic targets to curb HF in PWH.

Summary

During the past three decades, observational and mechanistic studies have provided important insights into risk factors and pathways that may contribute to the increased HF risk in PWH. Future work is needed to characterize these pathways more precisely in mechanistic studies of PWH, with the goal of ultimately deriving valuable targets for prevention, early diagnosis, and treatment of HF in PWH.

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Sinha, A., Feinstein, M.J. Immune Dysregulation in Myocardial Fibrosis, Steatosis, and Heart Failure: Current Insights from HIV and the General Population. Curr HIV/AIDS Rep 18, 63–72 (2021). https://doi.org/10.1007/s11904-020-00536-9

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