Lymphotoxin β receptor signaling promotes tertiary lymphoid organogenesis in the aorta adventitia of aged ApoE−/− mice

Atherosclerosis involves a macrophage-rich inflammation in the aortic intima. It is increasingly recognized that this intimal inflammation is paralleled over time by a distinct inflammatory reaction in adjacent adventitia. Though cross talk between the coordinated inflammatory foci in the intima and the adventitia seems implicit, the mechanism(s) underlying their communication is unclear. Here, using detailed imaging analysis, microarray analyses, laser-capture microdissection, adoptive lymphocyte transfers, and functional blocking studies, we undertook to identify this mechanism. We show that in aged apoE−/− mice, medial smooth muscle cells (SMCs) beneath intimal plaques in abdominal aortae become activated through lymphotoxin β receptor (LTβR) to express the lymphorganogenic chemokines CXCL13 and CCL21. These signals in turn trigger the development of elaborate bona fide adventitial aortic tertiary lymphoid organs (ATLOs) containing functional conduit meshworks, germinal centers within B cell follicles, clusters of plasma cells, high endothelial venules (HEVs) in T cell areas, and a high proportion of T regulatory cells. Treatment of apoE−/− mice with LTβR-Ig to interrupt LTβR signaling in SMCs strongly reduced HEV abundance, CXCL13, and CCL21 expression, and disrupted the structure and maintenance of ATLOs. Thus, the LTβR pathway has a major role in shaping the immunological characteristics and overall integrity of the arterial wall

Age-dependent differences in diabetes and acute hyperglycemia between men and women with ST-elevation myocardial infarction: a cohort study

Contains fulltext : 119180.pdf (publisher's version ) (Open Access)BACKGROUND: Both acute hyperglycemia as diabetes results in an impaired prognosis in ST-elevation myocardial infarction (STEMI) patients. It is unknown whether there is a different prevalence of diabetes and acute hyperglycemia in men and women within age-groups. METHODS: Between 2004 and 2010, 4640 consecutive patients (28% women) with STEMI, were referred for primary PCI. Patients were stratified into two age groups, /=65 years (2193 patients). Separate analyses were performed in 3901 patients without diabetes. Diabetes was defined as known diabetes or HbA1c >/=6.5 mmol/l at admission. RESULTS: The prevalence of diabetes was comparable between women and men in the younger age group (14% vs 12%, p = 0.52), whereas in the older age group diabetes was more prevalent in women (25% vs 17% p < 0.001). In patients without diabetes, admission glucose was comparable between both genders in younger patients (8.1 +/- 2.0 mmol/l vs 8.0 +/- 2.2 mmol/l p = 0.36), but in older patients admission glucose was higher in women than in men (8.7 +/- 2.1 mmol/l vs 8.4 +/- 2.1 mmol/l p = 0.028). After multivariable analyses, the occurrence of increased admission glucose was comparable between men and women in the younger age group (OR 1.1, 95%CI 0.9-1.5), but increased in women in the older age group (OR 1.3, 95% CI 1.1-1.7). Both diabetes and hyperglycemia were associated with a higher one-year mortality in both men and women. CONCLUSIONS: The differences between men and women in hyperglycemia and diabetes in patients with STEMI are age dependent and can only be observed in older patients. This may have implications for medical treatment and should be investigated further

Predictors of ventricular tachyarrhythmia in high-risk myocardial infarction patients treated with primary coronary intervention

Background. We investigated the association between clinical characteristics, angiographic data and ventricular arrhythmia in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI

A quantitative analysis of the effect of glucose-insulin-potassium in acute myocardial infarction

Objective. To review the currently available data to investigate the clinical benefit of high- and low-dose glucose-insulin-potassium (GIK) in patients with ST-segment elevation acute myocardial infarction (STEMI). Design. Quantitative analysis of all randomised trials on GIK in patients with STEMI. Electronic and manual searches for randomised controlled trials of GIK in STEMI were performed with regard to inclusion criteria, dose of GIK and additional use of reperfusion therapy, and a meta-analysis with the primary endpoint 30-day mortality was performed. Patients. Data from 16 randomised trials, involving 26,273 patients, were included. Results. Studies were conducted between 1962 and 2005. Overall, hospital mortality was 9.6% after GIK compared with 10.2% in controls (p=0.088). GIK infusion was not associated with an increase in major adverse events. Conclusion. This quantitative analysis of GIK in patients with STEMI did not show a beneficial or detrimental effect of GIK infusion on 30-day mortality. GIK infusion should not be part of the standard therapy for patients with STEM

A quantitative analysis of the effect of glucose-insulin-potassium in acute myocardial infarction

Objective. To review the currently available data to investigate the clinical benefit of high- and low-dose glucose-insulin-potassium (GIK) in patients with ST-segment elevation acute myocardial infarction (STEMI). Design. Quantitative analysis of all randomised trials on GIK in patients with STEMI. Electronic and manual searches for randomised controlled trials of GIK in STEMI were performed with regard to inclusion criteria, dose of GIK and additional use of reperfusion therapy, and a meta-analysis with the primary endpoint 30-day mortality was performed. Patients. Data from 16 randomised trials, involving 26,273 patients, were included. Results. Studies were conducted between 1962 and 2005. Overall, hospital mortality was 9.6% after GIK compared with 10.2% in controls (p=0.088). GIK infusion was not associated with an increase in major adverse events. Conclusion. This quantitative analysis of GIK in patients with STEMI did not show a beneficial or detrimental effect of GIK infusion on 30-day mortality. GIK infusion should not be part of the standard therapy for patients with STEM

Impact of diabetes on outcome in patients with non-ST-elevation myocardial infarction

Item does not contain fulltextBACKGROUND: Diabetes mellitus contributes to the increase of cardiovascular deaths worldwide. Despite continuous treatment evolution, patients with diabetes suffering from an acute coronary syndrome still have a high morbidity and mortality. We aimed to analyze the impact of diabetes on one-year outcome in an unselected patient population with non-ST-elevation myocardial infarction (non-STEMI). METHODS: Retrospective analysis of 847 unselected patients with non-STEMI. We compared the baseline characteristics, treatment and outcome of patients versus those without diabetes. RESULTS: A total of 138 patients had diabetes (16%) and 709 (84%) had no diabetes. Patients with diabetes were older, often had hypertension, hyperlipidemia, previous myocardial infarction and Killip class >/=2 on admission. Approximately 80% of both patients, with and without diabetes, underwent diagnostic coronary angiography. Multivessel disease was more present among patients with diabetes, but patients with diabetes were treated more often conservatively. At one-year follow up rates of death and major adverse cardiac events were significantly higher in patients with diabetes compared to those without diabetes (8% vs. 3%; P=0.001 and 23% vs. 14%; P=0.008, respectively). Even after adjustment for differences in baseline characteristics, diabetes remained an independent predictor of mortality (OR: 2.25; CI95%: 1.05-3.91). CONCLUSIONS: In an unselected patient population with non-STEMI, patients with diabetes have higher risk factors on admission, less often undergo coronary revascularisation and have worse outcome at one-year follow-up. Diabetes is an independent predictor of one-year mortality in patients with non-STEMI