RESUMO
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.
Assuntos
Arritmias Cardíacas/microbiologia , Cardiomegalia/microbiologia , Fibrose Endomiocárdica/microbiologia , Infecções por Mycobacterium não Tuberculosas/imunologia , Micobactérias não Tuberculosas , Envelhecimento/imunologia , Envelhecimento/patologia , Animais , Arritmias Cardíacas/genética , Arritmias Cardíacas/metabolismo , Cardiomegalia/genética , Cardiomegalia/metabolismo , Suscetibilidade a Doenças , Fibrose Endomiocárdica/genética , Fibrose Endomiocárdica/metabolismo , Feminino , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/imunologia , Inflamação/microbiologia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Antígenos Comuns de Leucócito/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Mycobacterium não Tuberculosas/patologia , Mycobacterium avium , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
We investigated hepatitis C virus (HCV) infection in 35 patients with hypertrophic cardiomyopathy and 40 patients with ischemic heart disease who were consecutively admitted to our hospital. Frequency of positive anti-HCV antibody was significantly higher in patients with hypertrophic cardiomyopathy (6 of 35 patients, 17.1%) than that in patients with ischemic heart disease (1 of 40 patients, 2.5%, p = 0.036). In three of these six patients with hypertrophic cardiomyopathy, HCV RNA was detected in myocardial tissue. In two of these three patients, HCV RNA was detected from biopsy and autopsy specimens of the ventricles, but not in the serum, suggesting that HCV may replicate in myocardial tissue and may be relevant to ventricular hypertrophy. Thus, HCV infection may play a role in the development of hypertrophic cardiomyopathy.