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Obesity superimposed on aging magnifies inflammation and delays the resolving response after myocardial infarction.

ABSTRACT: Polyunsaturated fatty acid (PUFA) intake has increased over the last 100 yr, contributing to the current obesogenic environment. Obesity and aging are prominent risk factors for myocardial infarction (MI). How obesity interacts with aging to alter the post-MI response, however, is unclear. We tested the hypothesis that obesity in aging mice would impair the resolution of post-MI inflammation. PUFA diet (PUFA aging group) feeding to 12-mo-old C57BL/6J mice for 5 mo showed higher fat mass compared with standard lab chow (LC)-fed young (LC young group; 3-5 mo old) or aging alone control mice (LC aging group). LC young, LC aging, and PUFA aging mice were subjected to coronary artery ligation to induce MI. Despite similar infarct areas post-MI, plasma proteomic profiling revealed higher VCAM-1 in the PUFA aging group compared with LC young and LC aging groups, leading to increased neutrophil infiltration in the PUFA aging group (P<0.05). Macrophage inflammatory protein-1? and CD40 were also increased at day 1, and myeloperoxidase remained elevated at day 5, an observation consistent with delayed wound healing in the PUFA aging group. Lipidomic analysis showed higher levels of arachidonic acid and 12(S)-hydroxyeicosatetraenoic acid at day 1 post-MI in the PUFA aging group compared with the LC aging group (all P<0.05), thereby mediating neutrophil extravasation in the PUFA aging group. The inflammation-resolving enzymes 5-lipoxygenase, cyclooxygenase-2, and heme oxyegnase-1 were altered to delay wound healing post-MI in the PUFA aging group compared with LC young and LC aging groups. PUFA aging magnifies the post-MI inflammatory response and impairs the healing response by stimulating prolonged neutrophil trafficking and proinflammatory lipid mediators.

SUBMITTER: Lopez EF

PROVIDER: S-EPMC4329482 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Obesity superimposed on aging magnifies inflammation and delays the resolving response after myocardial infarction.

Lopez Elizabeth F EF Kabarowski Janusz H JH Ingle Kevin A KA Kain Vasundhara V Barnes Stephen S Crossman David K DK Lindsey Merry L ML Halade Ganesh V GV

American journal of physiology. Heart and circulatory physiology 20141205 4

Polyunsaturated fatty acid (PUFA) intake has increased over the last 100 yr, contributing to the current obesogenic environment. Obesity and aging are prominent risk factors for myocardial infarction (MI). How obesity interacts with aging to alter the post-MI response, however, is unclear. We tested the hypothesis that obesity in aging mice would impair the resolution of post-MI inflammation. PUFA diet (PUFA aging group) feeding to 12-mo-old C57BL/6J mice for 5 mo showed higher fat mass compared ...[more]

PMID: 25485899

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Project description:BackgroundPreclinical data suggest that an acute inflammatory response following myocardial infarction (MI) accelerates systemic atherosclerosis. Using combined positron emission and computed tomography, we investigated whether this phenomenon occurs in humans.Methods and resultsOverall, 40 patients with MI and 40 with stable angina underwent thoracic 18F-fluorodeoxyglucose combined positron emission and computed tomography scan. Radiotracer uptake was measured in aortic atheroma and nonvascular tissue (paraspinal muscle). In 1003 patients enrolled in the Global Registry of Acute Coronary Events, we assessed whether infarct size predicted early (≤30 days) and late (>30 days) recurrent coronary events. Compared with patients with stable angina, patients with MI had higher aortic 18F-fluorodeoxyglucose uptake (tissue-to-background ratio 2.15±0.30 versus 1.84±0.18, P<0.0001) and plasma C-reactive protein concentrations (6.50 [2.00 to 12.75] versus 2.00 [0.50 to 4.00] mg/dL, P=0.0005) despite having similar aortic (P=0.12) and less coronary (P=0.006) atherosclerotic burden and similar paraspinal muscular 18F-fluorodeoxyglucose uptake (P=0.52). Patients with ST-segment elevation MI had larger infarcts (peak plasma troponin 32 300 [10 200 to >50 000] versus 3800 [1000 to 9200] ng/L, P<0.0001) and greater aortic 18F-fluorodeoxyglucose uptake (2.24±0.32 versus 2.02±0.21, P=0.03) than those with non-ST-segment elevation MI. Peak plasma troponin concentrations correlated with aortic 18F-fluorodeoxyglucose uptake (r=0.43, P=0.01) and, on multivariate analysis, independently predicted early (tertile 3 versus tertile 1: relative risk 4.40 [95% CI 1.90 to 10.19], P=0.001), but not late, recurrent MI.ConclusionsThe presence and extent of MI is associated with increased aortic atherosclerotic inflammation and early recurrent MI. This finding supports the hypothesis that acute MI exacerbates systemic atherosclerotic inflammation and remote plaque destabilization: MI begets MI.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01749254.

Project description:Inflammation is associated with increased sympathetic drive in cardiovascular diseases. Blood-borne proinflammatory cytokines, markers of inflammation, induce cyclooxygenase 2 (COX-2) activity in perivascular macrophages of the blood-brain barrier. COX-2 generates prostaglandin E(2), which may enter the brain and increase sympathetic nerve activity. We examined the contribution of this mechanism to augmented sympathetic drive in rats after myocardial infarction (MI). Approximately 24 hours after acute MI, rats received an intracerebroventricular injection (1 microL/min over 40 minutes) of clodronate liposomes (MI+CLOD) to eliminate brain perivascular macrophages, liposomes alone, or artificial cerebrospinal fluid. A week later, COX-2 immunoreactivity in perivascular macrophages and COX-2 mRNA and protein had increased in hypothalamic paraventricular nucleus of MI rats treated with artificial cerebrospinal fluid or liposomes alone compared with sham-operated rats. In MI+CLOD rats, neither perivascular macrophages nor COX-2 immunoreactivity was seen in the paraventricular nucleus, and COX-2 mRNA and protein levels were similar to those in sham-operated rats. Prostaglandin E(2) in cerebrospinal fluid, paraventricular nucleus neuronal excitation, and plasma norepinephrine were less in MI+CLOD rats than in MI rats treated with artificial cerebrospinal fluid or liposomes alone but more than in sham-operated rats. Intracerebroventricular CLOD had no effect on interleukin 1beta and tumor necrosis factor-alpha mRNA and protein in the paraventricular nucleus or plasma interleukin-1beta and tumor necrosis factor-alpha, which were increased in MI compared with sham-operated rats. In normal rats, pretreatment with intracerebroventricular CLOD reduced (P<0.05) the renal sympathetic, blood pressure, and heart rate responses to intracarotid artery injection of tumor necrosis factor-alpha (0.5 microg/kg); intracerebroventricular liposomes had no effect. The results suggest that proinflammatory cytokines stimulate sympathetic excitation after MI by inducing COX-2 activity and prostaglandin E(2) production in perivascular macrophages of the blood-brain barrier.

Project description:BackgroundSystemic immune inflammatory index (SII) and systemic inflammatory response index (SIRI) are combinations of non-specific inflammatory and adaptive immune response impairments associated with cardiovascular disease. Yet little analysis has been done on SII, SIRI and acute myocardial infarction (AMI) prognosis. The purpose of this study was to investigate the correlation of SII and SIRI with clinical risk factors such as GRACE, Gensini, and QTc after acute myocardial infarction.MethodsThis study enrolled 310 patients with AMI from February 1, 2018, to December 31, 2022, at our institution. Routine blood items calculated SII and SIRI. Two groups were divided according to whether MACE occurred: the MACE group (81 cases) and the NMACE group (229 cases); each group was divided into three groups according to the SII and SIRI tertiles. The relationship between SII, SIRI and MACE was analyzed using multifactorial logistic regression analysis after adjusting for confounders; ROC curves were plotted to examine the predictive value of SII and SIRI for MACE. The correlation between SII and SIRI and potential risk factors such as Gensini, QTc and GRACE was further analyzed.ResultsThe study enrolled 310 patients, comprising 248 men (80%, mean age 60.73 ± 13.695 years) and 62 women (20%, mean age 69.79 ± 11.555 years). In the regression model completely adjusted for confounders, the risk of MACE was higher in AMI patients with SII > 11.00 [OR = 1.061,95% CI (1.018,1.105)] than in SII < 5.98; the risk of MACE was 115.3% higher in AMI patients with SIRI (1.72-3.68) [OR = 2.153, 95% CI (1.251, 3.705)] was 115.3% higher in AMI patients with SIRI < 1.72 and the risk of MACE was 25.1% higher in AMI patients with SIRI > 3.68 [OR = 1.251, 95% CI (1.123, 1.394)] than in AMI patients with SIRI < 1.72. In addition, SII, SIRI, and potential post-infarction risk factors (Gensini, QTc, and GRACE) were also associated.ConclusionSII and SIRI have been significantly associated with post-myocardial infarction MACE and the predictive potential clinically integrated risk factors in AMI patients, for which more attention should be paid to targeted anti-inflammatory therapy in AMI patients to further reduce the incidence of prognostic MACE in AMI patients.

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Obesity superimposed on aging magnifies inflammation and delays the resolving response after myocardial infarction.

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Obesity superimposed on aging magnifies inflammation and delays the resolving response after myocardial infarction.

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