ABSTRACT
Biological aging dynamically alters normal immune and cardiac function, favoring the production of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and increased instances of cardiac distress. Cardiac failure is the primary reason for hospitalization of the elderly (65+ years). The elderly are also increasingly susceptible to developing chronic bacterial infections due to aging associated immune abnormalities. Since bacterial infections compound the rates of cardiac failure in the elderly, and this phenomenon is not entirely understood, the interplay between the immune system and cardiovascular function in the elderly is of great interest. Using Mycobacterium avium, an opportunistic pathogen, we investigated the effect of mycobacteria on cardiac function in aged mice. Young (2-3 months) and old (18-20 months) C57BL/6 mice were intranasally infected with M. avium strain 104, and we compared the bacterial burden, immune status, cardiac electrical activity, pathology, and function of infected mice against uninfected age-matched controls. Herein, we show that biological aging may predispose old mice infected with M. avium to mycobacterial dissemination into the heart tissue and this leads to cardiac dysfunction. M. avium infected old mice had significant dysrhythmia, cardiac hypertrophy, increased recruitment of CD45+ leukocytes, cardiac fibrosis, and increased expression of inflammatory genes in isolated heart tissue. This is the first study to report the effect of mycobacteria on cardiac function in an aged model. Our findings are critical to understanding how nontuberculous mycobacterium (NTM) and other mycobacterial infections contribute to cardiac dysfunction in the elderly population.
Subject(s)
Arrhythmias, Cardiac/microbiology , Cardiomegaly/microbiology , Endomyocardial Fibrosis/microbiology , Mycobacterium Infections, Nontuberculous/immunology , Nontuberculous Mycobacteria , Aging/immunology , Aging/pathology , Animals , Arrhythmias, Cardiac/genetics , Arrhythmias, Cardiac/metabolism , Cardiomegaly/genetics , Cardiomegaly/metabolism , Disease Susceptibility , Endomyocardial Fibrosis/genetics , Endomyocardial Fibrosis/metabolism , Female , Gene Expression Regulation/genetics , Gene Expression Regulation/immunology , Inflammation/microbiology , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Leukocyte Common Antigens/immunology , Mice , Mice, Inbred C57BL , Mycobacterium Infections, Nontuberculous/pathology , Mycobacterium avium , Signal Transduction/genetics , Signal Transduction/immunology , Tumor Necrosis Factor-alpha/metabolismSubject(s)
Endomyocardial Fibrosis , Eosinophilia , Magnetic Resonance Imaging , Adult , Bacteremia , Catheterization, Central Venous/adverse effects , Endomyocardial Fibrosis/microbiology , Endomyocardial Fibrosis/pathology , Fatal Outcome , Humans , Lymphoma/complications , Lymphoma/drug therapy , Male , Staphylococcal Infections , Staphylococcus aureusABSTRACT
This article reviews cardiac manifestations of AIDS in terms of etiology, pathogenesis, pathoanatomic lesions and heart function. Hypothetically the prevalence of myocarditis and disperse fibrosis of the myocardium are correlated to increasing rates of dilated cardiomyopathy and cardiac insufficiency. Echocardiography has proved to be of value in detecting early abnormalities and should be recommended on broad indications, though aggressive therapy of cardiac abnormalities is of importance to ensure quality of life and surveillance for the patients.
