Monocytes/macrophages prevent healing defects and left ventricular thrombus formation after myocardial infarction.

Myocardial infarction (MI) leads to rapid necrosis of cardiac myocytes. To achieve tissue integrity and function, inflammatory cells are activated, including monocytes/macrophages. However, the effect of monocyte/macrophage recruitment after MI remains poorly defined. After experimental MI, monocytes and macrophages were depleted through serial injections of clodronate-containing liposomes. Monocyte/macrophage infiltration was reduced in the myocardium after MI by active treatment. Mortality was increased due to thromboembolic events in monocyte- and macrophage-depleted animals (92 vs. 33%; P<0.01). Left ventricular thrombi were detectable as early as 24 h after MI; this was reproduced in a genetic model of monocyte/macrophage ablation. A general prothrombotic state, increased infarct expansion, and deficient neovascularization were not observed. Severely compromised extracellular matrix remodeling (collagen I, placebo liposome vs. clodronate liposome, 2.4 ± 0.2 vs. 0.8 ± 0.2 arbitrary units; P<0.001) and locally lost integrity of the endocardium after MI are potential mechanisms. Patients with a left ventricular thrombus had a relative decrease of CD14CD16 monocyte/macrophage subsets in the peripheral blood after MI (no thrombus vs. thrombus, 14.2 ± 0.9 vs. 7.80 ± 0.4%; P<0.05). In summary, monocytes/macrophages are of central importance for healing after MI. Impaired monocyte/macrophage function appears to be an unrecognized new pathophysiological mechanism for left ventricular thrombus development after MI.

Moderate and severe periodontitis are independent risk factors associated with low cardiorespiratory fitness in sedentary non-smoking men aged between 45 and 65 years.

AIM: To investigate the association between periodontal disease severity and cardiorespiratory fitness (CRF) in a cross-sectional study of sedentary men. MATERIALS & METHODS: Seventy-two healthy men (45-65 years) who did not join any sport activity and had a preferentially sitting working position were recruited. Periodontal status was recorded and CRF was measured by peak oxygen uptake (VO2 peak ) during exercise testing on a cycle ergometer. Physical activity was assessed by a validated questionnaire and data were transformed to metabolic equivalent of task scores. Univariate and multivariate regression analyses were performed to investigate associations. RESULTS: Differences between VO2 peak levels in subjects with no or mild, moderate or severe periodontitis were statistically significant (p = 0.026). Individuals with low VO2 peak values showed high BMI scores, high concentrations of high-sensitive C-reactive protein, low levels of high-density lipoprotein-cholesterol, and used more glucocorticoids compared to individuals with high VO2 peak levels. Multivariate regression analysis showed that high age (p = 0.090), high BMI scores (p < 0.001), low levels of physical activity (p = 0.031) and moderate (p = 0.087), respectively, severe periodontitis (p = 0.033) were significantly associated with low VO2 peak levels. CONCLUSIONS: This study demonstrated that moderate and severe periodontitis were independently associated with low levels of CRF in sedentary men aged between 45 and 65 years.

Macrophage Mineralocorticoid Receptor Is a Pleiotropic Modulator of Myocardial Infarct Healing.

Myocardial infarction (MI) is a major cause of death worldwide. Here, we identify the macrophage MR (mineralocorticoid receptor) as a crucial pathogenic player in cardiac wound repair after MI. Seven days after left coronary artery ligation, mice with myeloid cell-restricted MR deficiency compared with WT (wild type) controls displayed improved cardiac function and remodeling associated with enhanced infarct neovascularization and scar maturation. Gene expression profiling of heart-resident and infarct macrophages revealed that MR deletion drives macrophage differentiation in the ischemic microenvironment toward a phenotype outside the M1/M2 paradigm, with regulation of multiple interrelated factors controlling wound healing and tissue repair. Mechanistic and functional data suggest that inactivation of the macrophage MR promotes myocardial infarct healing through enhanced efferocytosis of neutrophils, the suppression of free radical formation, and the modulation of fibroblast activation state. Crucially, targeted delivery of MR antagonists to macrophages, with a single administration of RU28318 or eplerenone-containing liposomes at the onset of MI, improved the healing response and protected against cardiac remodeling and functional deterioration, offering an effective and unique therapeutic strategy for cardiac repair.