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Myocardial lipofuscin accumulation in ageing and sudden cardiac death.

ABSTRACT: Lipofuscin is an intracellular aggregate of highly oxidized proteins that cannot be digested in the ubiquitin-proteasome system and accumulate mainly in lysosomes, especially in aged cells and pathological conditions. However, no systematic study has evaluated the cardiac accumulation of lipofuscin during human ageing and sudden cardiac death (SCD). Age estimation in unidentified bodies and postmortem SCD diagnosis are important themes in forensics. Thus, we aimed to elucidate their correlations with myocardial lipofuscin accumulation. We collected 76 cardiac samples from autopsy patients aged 20-97 years. After histopathological examination, myocardial lipofuscin was measured using its autofluorescence. Lipofuscin accumulated mainly in the perinuclear zone, and its accumulation rate positively correlated with chronological ageing (r?=?0.82). Meanwhile, no significant change in lipofuscin level was observed with different causes of death, including SCD. There was also no significant change in lipofuscin level in relation to body mass index, serum brain natriuretic peptide level, or heart weight. Moreover, we performed LC3 and p62 immunoblotting to evaluate autophagic activity, and no change was observed in ageing. Therefore, lipofuscin accumulation more directly reflects chronological ageing rather than human cardiac pathology. Our study reveals the stability and utility of cardiac lipofuscin measurement for age estimation during autopsy.

SUBMITTER: Kakimoto Y

PROVIDER: S-EPMC6397159 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Myocardial lipofuscin accumulation in ageing and sudden cardiac death.

Kakimoto Yu Y Okada Chisa C Kawabe Noboru N Sasaki Ayumi A Tsukamoto Hideo H Nagao Ryoko R Osawa Motoki M

Scientific reports 20190301 1

Lipofuscin is an intracellular aggregate of highly oxidized proteins that cannot be digested in the ubiquitin-proteasome system and accumulate mainly in lysosomes, especially in aged cells and pathological conditions. However, no systematic study has evaluated the cardiac accumulation of lipofuscin during human ageing and sudden cardiac death (SCD). Age estimation in unidentified bodies and postmortem SCD diagnosis are important themes in forensics. Thus, we aimed to elucidate their correlations ...[more]

PMID: 30824797

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Project description:BackgroundThe incidence of sudden cardiac death and sudden death caused by arrhythmia, as determined by autopsy, in persons with human immunodeficiency virus (HIV) infection has not been clearly established.MethodsBetween February 1, 2011, and September 16, 2016, we prospectively identified all new deaths due to out-of-hospital cardiac arrest among persons 18 to 90 years of age, with or without known HIV infection, for comprehensive autopsy and toxicologic and histologic testing. We compared the rates of sudden cardiac death and sudden death caused by arrhythmia between groups.ResultsOf 109 deaths from out-of-hospital cardiac arrest among 610 unexpected deaths in HIV-positive persons, 48 met World Health Organization criteria for presumed sudden cardiac death; of those, fewer than half (22) had an arrhythmic cause. A total of 505 presumed sudden cardiac deaths occurred between February 1, 2011, and March 1, 2014, in persons without known HIV infection. Observed incidence rates of presumed sudden cardiac death were 53.3 deaths per 100,000 person-years among persons with known HIV infection and 23.7 deaths per 100,000 person-years among persons without known HIV infection (incidence rate ratio, 2.25; 95% confidence interval [CI], 1.37 to 3.70). Observed incidence rates of sudden death caused by arrhythmia were 25.0 and 13.3 deaths per 100,000 person-years, respectively (incidence rate ratio, 1.87; 95% CI, 0.93 to 3.78). Among all presumed sudden cardiac deaths, death due to occult drug overdose was more common in persons with known HIV infection than in persons without known HIV infection (34% vs. 13%). Persons who were HIV-positive had higher histologic levels of interstitial myocardial fibrosis than persons without known HIV infection.ConclusionsIn this postmortem study, the rates of presumed sudden cardiac death and myocardial fibrosis were higher among HIV-positive persons than among those without known HIV infection. One third of apparent sudden cardiac deaths in HIV-positive persons were due to occult drug overdose. (Supported by the National Heart, Lung, and Blood Institute.).

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Myocardial lipofuscin accumulation in ageing and sudden cardiac death.

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Myocardial lipofuscin accumulation in ageing and sudden cardiac death.

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