Monocytes: Protagonists of Infarct Inflammation and Repair After Myocardial Infarction

Nahrendorf, Matthias; Pittet, Mikaël J.; Świrski, Filip K.

doi:10.1161/circulationaha.109.916346

Cited by 687 publications

(642 citation statements)

References 103 publications

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“…Inflammation plays a critical role in the development of coronary heart disease and is centrally involved in healing after MI (28). While invading leukocytes are essential for the removal of debris and dead tissue, an excessive production of myeloid cells is associated with an impaired development of cardiac function and outcome (12,29,30).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic hypothermia impacts leukocyte kinetics after cardiac arrest

Dufner

André

Stiepak³

et al. 2016

Cardiovasc. Diagn. Ther.

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Background: Patients admitted to the hospital after primarily successful cardiopulmonary resuscitation (CPR) are at a very high risk for neurologic deficits and death. Targeted temperature management (TTM) for mild therapeutic hypothermia has been shown to improve survival compared to standard treatment.Acute cardiovascular events, such as myocardial infarction (MI), are a major cause for cardiac arrest (CA) in patients who undergo CPR. Recent findings have demonstrated the importance and impact of the leukocyte response following acute MI.Methods: In this retrospective, single center study we enrolled 169 patients with CA due to non-traumatic causes and primarily successful CPR. A total of 111 subjects (66%) underwent TTM aiming for a target temperature of 32-34 ℃.Results: Analysis of 30 day follow up showed a significantly improved survival of all patients who received TTM compared to patients without hypothermia (P=0.0001). Furthermore TTM was an independent variable of good neurological outcome after 6 months (P=0.0030). Therapeutic hypothermia was found to be beneficial independent of differences in age and sex between both groups. While a higher rate of pneumonia was observed with TTM, this diagnosis had no additional impact on survival or neurological outcome. The beneficial effect on mortality remained significant in patients with the diagnosis of an acute cardiac event (P=0.0145). Next, we evaluated the kinetics of leukocytes in this group over the course of 7 days after CA.At presentation, patients showed a mean level of 16.5±6.7 of leukocytes per microliter. While this level stayed stable in the group of patients without hypothermia, patients who received TTM showed a significant decline of leukocyte levels resulting in significantly lower numbers of leukocytes on days 3 and 5 after CPR. Interestingly, these differences in leukocyte counts remained beyond the time period of TTM while C-reactive protein (CRP) levels were suppressed only during ongoing cooling, but differences between the groups were diminished after TTM was terminated (from day 3 on, P>0.2). Finally, patients who received TTM and showed a leukocyte count of less than 12.7/μL on day 3 had an improved survival (P=0.0214) and neurological outcome (P=0.0049) compared to patients above that level.Conclusions: Our data underline the beneficial effects of TTM and demonstrate an impact of hypothermia on leukocyte counts after CA.

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Section: Discussionmentioning

confidence: 99%

Therapeutic hypothermia impacts leukocyte kinetics after cardiac arrest

Dufner

André

Stiepak³

et al. 2016

Cardiovasc. Diagn. Ther.

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“…Isolated mononuclear cells were then incubated with PerCP/Cy5. 5 Chemokine levels of CCL2 in the serum were measured using the human ELISA Ready-SET-Go kit (R&D Systems Inc.) according to the manufacturer's protocol. The absorbance of the test sample was compared with the standard curve.…”

Section: Methodsmentioning

confidence: 99%

“…The prevailing belief is that circulating monocytes are relatively uncommitted and that their eventual phenotype entirely depends on the tissue environment. 5) In mice, one subset of monocytes (Ly-6C hi ) aggravates inflammation and expands in AMI conditions, whereas another subset of monocytes (Ly-6C low ) attenuates inflammation and promotes angiogenesis and granulation tissue formation in the process. In humans, monocytes have recently been defined and divided into three subsets 6,7) : (1) "classical" monocytes (CD14 ++ CD16 -; also referred to as Mon1), which account for 80% to 85% in the total population of circulating monocytes; (2) CD14 + CD16…”

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confidence: 99%

Intermediate Monocytes Lead to Enhanced Myocardial Remodelling in STEMI Patients With Diabetes

Zhang

2015

Int. Heart J.

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SummaryThis study aimed to evaluate the potential associations of intermediate monocytes (CD14 ++ CD16 + ) with myocardial remodelling in ST segment elevation myocardial infarction (STEMI) patients with diabetes.A total of 67 STEMI patients with diabetes were enrolled. The control group consisted of 65 STEMI patients without diabetes. All patients received emergency medical services for reperfusion therapy in less than 12 hours after onset of AMI. Blinded to patient clinical characteristics, monocyte subset analysis was performed using flow cytometry immediately after admission. mRNA of Chemokine Decoy Receptor D6 in each subset of monocytes was validated by Q-PCR. Expression of CCL2 in patient plasma was determined with an Elisa kit. Infarct size and left ventricular ejection fraction (LVEF) were measured using 3-dimensional echocardiography 3 days and 6 months after AMI. The incidences of recurrent cardiovascular events and death in each group were measured using the Kaplan-Meier estimator in follow-up during the next 24 months. Cox proportional-hazard models were further used to analyze the relationship of monocyte cell counts and event-free survival after adjusting for confounding factors.The number of circulating intermediate monocytes was significantly correlated with LVEF% and infarct size (r = -0.32; P = 0.008; r = 0.57, P < 0.001) in STEMI patients with diabetes compared with those without diabetes 6 months after AMI. Chemokine Decoy Receptor D6 transcript levels were lower in intermediate monocytes of STEMI patients with diabetes compared to the subsets in STEMI patients without diabetes (P < 0.001). Higher levels of CCL2 (pg/mL) were observed in STEMI patients with diabetes compared to STEMI patients without diabetes (P < 0.001). During a mean follow-up period of 24 ± 1 month, recurrent cardiovascular events or death occurred in 23 patients belonging to the STEMI with diabetes group and 10 belonging to the control group. Univariate Kaplan-Meier analysis revealed that counts of the intermediate monocytes according to median showed statistical significance in STEMI patients with diabetes (P = 0.010). After full adjustment for confounding factors, the cells were found to remain independently related to recurrent cardiovascular events or death in this group (P = 0.004, 95% CI: 1.62-12.49).Intermediate monocytes were associated with LV remodelling in STEMI patients with diabetes. The cells were predictive for recurrent cardiovascular events or death in these patients. A low level of D6 mRNA in the intermediate monocytes of STEMI patients with diabetes and high level of CCL2 in these patients may partially explain the causality. (Int Heart J 2015; 56: 22-28)

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“…The distribution of serum ferritin for cases and controls indicated a shift towards higher concentration in patients with AMI. 27 Experimental studies have shown that short periods of ischemia followed by reperfusion elicit a cascade of pro inflammatory reactions that include production of oxygen-derived free radicals, activation of the complement system, adherence of the neutrophils to the coronary endothelium, leukocytemediated injury of the myocardial cells, and production of cytokines and acute phase proteins. 28 High sensitivity testing for CRP (hsCRP) has emerged as a convenient tool for detecting low-level systemic inflammation that portends a higher risk of developing atherothrombotic vascular disease in ostensibly healthy men and women and poor short-and long-term prognosis in patients after AMI.…”

Section: Resultsmentioning

confidence: 99%