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

Sinha, Arjun; Feinstein, Matthew J.

doi:10.1007/s11904-020-00536-9

Cited by 8 publications

(5 citation statements)

References 81 publications

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“…Further corroboration of this view comes from the observation that treatment with different antibiotics, which variably affects the relative abundance of different gut microbial species, reduces gut microbial diversity and leads to abnormal gut barrier integrity, rather than the specific bacterial taxa. In light of these considerations, we hypothesized that a reduction in microbial diversity might underlie the known disturbances in gut barrier integrity seen in virally suppressed PWH despite viral suppression and immune recovery [27]. We used plasma occludin levels as an index of abnormal gut barrier integrity, based on the notion that compromise of the gut barrier leads to compensatory overexpression of occludin to facilitate tightening of the barrier [28].…”

Section: Introductionmentioning

confidence: 99%

Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV

Ellis

Iudicello

Heaton

et al. 2021

Viruses

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People with human immunodeficiency virus (HIV) (PWH) have reduced gut barrier integrity (“leaky gut”) that permits diffusion of microbial antigens (microbial translocation) such as lipopolysaccharide (LPS) into the circulation, stimulating inflammation. A potential source of this disturbance, in addition to gut lymphoid tissue CD4+ T-cell depletion, is the interaction between the gut barrier and gut microbes themselves. We evaluated the relationship of gut barrier integrity, as indexed by plasma occludin levels (higher levels corresponding to greater loss of occludin from the gut barrier), to gut microbial diversity. PWH and people without HIV (PWoH) participants were recruited from community sources and provided stool, and 16S rRNA amplicon sequencing was used to characterize the gut microbiome. Microbial diversity was indexed by Faith’s phylogenetic diversity (PD). Participants were 50 PWH and 52 PWoH individuals, mean ± SD age 45.6 ± 14.5 years, 28 (27.5%) women, 50 (49.0%) non-white race/ethnicity. PWH had higher gut microbial diversity (Faith’s PD 14.2 ± 4.06 versus 11.7 ± 3.27; p = 0.0007), but occludin levels were not different (1.84 ± 0.311 versus 1.85 ± 0.274; p = 0.843). Lower gut microbial diversity was associated with higher plasma occludin levels in PWH (r = −0.251; p = 0.0111), but not in PWoH. A multivariable model demonstrated an interaction (p = 0.0459) such that the correlation between Faith’s PD and plasma occludin held only for PWH (r = −0.434; p = 0.0017), but not for PWoH individuals (r = −0.0227; p = 0.873). The pattern was similar for Shannon alpha diversity. Antiretroviral treatment and viral suppression status were not associated with gut microbial diversity (ps > 0.10). Plasma occludin levels were not significantly related to age, sex or ethnicity, nor to current or nadir CD4 or plasma viral load. Higher occludin levels were associated with higher plasma sCD14 and LPS, both markers of microbial translocation. Together, the findings suggest that damage to the gut epithelial barrier is an important mediator of microbial translocation and inflammation in PWH, and that reduced gut microbiome diversity may have an important role.

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Section: Introductionmentioning

confidence: 99%

Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV

Ellis

Iudicello

Heaton

et al. 2021

Viruses

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“…In recent years, the prevalence and mortality of HF have increased. Controlling HF risk factors and actively treating asymptomatic left ventricular systolic dysfunction can delay or even prevent the occurrence of HF (Sinha & Feinstein, 2021). Therefore, it is recommended to follow the HF guidelines for diagnosis and treatment, and to identify the cause of HF in patients and control risk factors, and take specific or targeted treatment as soon as possible, which will help improve the survival and quality of life of patients (Neilan et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

HIV infection and risk of heart failure: A meta-analysis and systematic review

Li¹

2022

Acta Biochim Pol

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Background: Heart failure (HF) is commonly seen in patients with human immunodeficiency virus (HIV) infection. We aimed to evaluate the potential correlations of HIV infection and risk of HF, to provide evidence to the management of HIV and HF. Methods: We searched PubMed and other databases to identify prospective cohort studies on the risk of HIV infection and heart failure, we used Stata 13 software for Meta-analysis, and we calculated the hazard ratio (HR) values and 95% confidence interval (CI) values for the risks of HF in patients with and without HIV infections. Results: A total of five studies were included, with 8457 cases in the HIV-infection and 21917 cases in the non-HIV-infection group. Meta-analysis results showed that HIV infection can increase the risk of HF by 48% (HR=1.48, 95% CI1.31~1.67). Subgroups analyses by HIV-1 RNA viral load, CD4+ cell count, and study population also favored the overall results, and the research heterogeneity mainly come from the group of veterans in the research population. Conclusions: HIV infection is one of the risk factors for HF, which can increase the risk of heart failure, early preventions and interventions are needed for those populations.

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“…90,91,101 The mechanisms by which HIV increases myocardial steatosis are likely multifactorial, but may entail immune activation, increased oxidative stress, derangements in lipid metabolism, and injury and dysfunction of resident adipose tissue within and around the heart. 105 The net result is likely an interconnected and bidirectional relationship between myocardial steatosis, inflammation, and fibrosis that impairs cardiac function and increases risk for adverse outcomes.…”

Section: Myocardial Structural Pathologymentioning

confidence: 99%

Cardiovascular Disease Among Persons Living With HIV: New Insights Into Pathogenesis and Clinical Manifestations in a Global Context

Ntsekhe

Baker

2023

Circulation

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Widespread use of contemporary antiretroviral therapy globally has transformed HIV disease into a chronic illness associated with excess risk for disorders of the heart and circulatory system. Current clinical care and research has focused on improving HIV-related cardiovascular disease outcomes, survival, and quality of life. In high-income countries, emphasis on prevention of atherosclerotic coronary artery disease over the past decade, including aggressive management of traditional risk factors and earlier initiation of antiretroviral therapy, has reduced risk for myocardial infarction among persons living with human immunodeficiency virus-1 infection. Still, across the globe, persons living with human immunodeficiency virus-1 infection on effective antiretroviral therapy treatment remain at increased risk for ischemic outcomes such as myocardial infarction and stroke relative to the persons without HIV. Unique features of HIV-related cardiovascular disease, in part, include the pathogenesis of coronary disease characterized by remodeling ectasia and unusual plaque morphology, the relative high proportion of type 2 myocardial infarction events, abnormalities of the aorta such as aneurysms and diffuse aortic inflammation, and HIV cerebrovasculopathy as a contributor to stroke risk. Literature over the past decade has also reflected a shift in the profile and prevalence of HIV-associated heart failure, with a reduced but persistent risk of heart failure with reduced ejection fraction and a growing risk of heart failure with preserved ejection fraction. Cardiac magnetic resonance imaging and autopsy data have emphasized the central importance of intramyocardial fibrosis for the pathogenesis of both heart failure with preserved ejection fraction and the increase in risk of sudden cardiac death. Still, more research is needed to better characterize the underlying mechanisms and clinical phenotype of HIV-associated myocardial disease in the current era. Across the different cardiovascular disease manifestations, a common pathogenic feature is that HIV-associated inflammation working through different mechanisms may amplify underlying pathology because of traditional risk and other host factors. The prevalence and phenotype of individual cardiovascular disease manifestations is ultimately influenced by the degree of injury from HIV disease combined with the profile of underlying cardiometabolic factors, both of which may differ substantially by region globally.

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

Cited by 8 publications

References 81 publications

Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV

Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV

HIV infection and risk of heart failure: A meta-analysis and systematic review

Cardiovascular Disease Among Persons Living With HIV: New Insights Into Pathogenesis and Clinical Manifestations in a Global Context

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