Excessive Adventitial and Perivascular Vascularisation Correlates with Vascular Inflammation and Intimal Hyperplasia.

Albeit multiple studies demonstrated that vasa vasorum (VV) have a crucial importance in vascular pathology, the informative markers and metrics of vascular inflammation defining the development of intimal hyperplasia (IH) have been vaguely studied. Here, we employed two rat models (balloon injury of the abdominal aorta and the same intervention optionally complemented with intravenous injections of calciprotein particles) and a clinical scenario (arterial and venous conduits for coronary artery bypass graft (CABG) surgery) to investigate the pathophysiological interconnections among VV, myeloperoxidase-positive (MPO+) clusters, and IH. We found that the amounts of VV and MPO+ clusters were strongly correlated; further, MPO+ clusters density was significantly associated with balloon-induced IH and increased at calciprotein particle-provoked endothelial dysfunction. Likewise, number and density of VV correlated with IH in bypass grafts for CABG surgery at the pre-intervention stage and were higher in venous conduits which more frequently suffered from IH as compared with arterial grafts. Collectively, our results underline the pathophysiological importance of excessive VV upon the vascular injury or at the exposure to cardiovascular risk factors, highlight MPO+ clusters as an informative marker of adventitial and perivascular inflammation, and propose another mechanistic explanation of a higher long-term patency of arterial grafts upon the CABG surgery.

Screening for Glucose Metabolism Disorders, Assessment the Disse Insulin Resistance Index and Hospital Prognosis of Coronary Artery Bypass Surgery.

OBJECTIVE: To study insulin resistance markers and their relationship with preoperative status and hospital complications of coronary artery bypass grafting (CABG) in patients with type 2 diabetes, prediabetes and normoglycemia. METHODS: We included 383 consecutive patients who underwent CABG. Patients were divided into two groups-with carbohydrate metabolism disorders (CMD, n = 192) and without CMD (n = 191). Free fatty acids and fasting insulin in plasma were determined, and the Disse, QUICKI and revised QUICKI indices were calculated in all patients. Perioperative characteristics and postoperative complications were analyzed in these groups, and their relations with markers of insulin resistance. RESULTS: Screening before CABG increased the number of patients with CMD from 25.3% to 50.1%. Incidence of postoperative stroke (p = 0.044), and hospital stay after CABG > 30 days (p = 0.014) was greater in CMD patients. Logistic regression analysis revealed that an increase in left atrial size, age, aortic clamping time, and decrease in Disse index were independently associated with hospital stay >10 days and/or perioperative complications. CONCLUSIONS: Screening for CMD before CABG increased the patient number with prediabetes and type 2 diabetes. In the CMD group, there were more frequent hospital complications. The Disse index was an independent predictor of long hospital stay and/or poor outcomes.

Mitomycin C induced genotoxic stress in endothelial cells is associated with differential expression of proinflammatory cytokines.

Mitomycin C (MMC) is an alkylating chemotherapy drug that causes DNA crosslinking resulting in transcription arrest and apoptosis. DNA crosslinking is a critical damage to DNA that can be caused not only by MMC and other antitumor drugs, but also by various environmental and anthropogenic endo- and exogenous agents. Mammalian cells exposed to alkylating mutagens are characterized by severe genotoxic stress. Somatic mutations and genotoxic stress may lead to endothelial dysfunction, which is the initial stage of atherosclerosis, a leading cause of morbidity and mortality worldwide. Here we studied DNA damage, protein secretion and gene expression of IL6 and IL8 in primary human coronary artery endothelial cells (HCAEC) and human internal thoracic artery endothelial cells (HITAEC) in vitro exposed to 500 ng/mL MMC. We observed an increase in levels of cytogenetic damage (micronuclei, nucleoplasmic bridges and nuclear buds) in MMC-treated cells compared to control cells. After 6 h incubation with MMC, both HCAEC and HITAEC displayed a decrease in IL8 concentration and the mRNA level of IL6 and IL8 compared to control cells. Removal of MMC from cultures after 6 h followed by 24 h incubation of cells in complete growth media led to a sharp increase in secretion and gene expression of the studied cytokines in both HCAEC and HITAEC. Moreover, HCAEC were more susceptible to mutagenic exposure compared to HITAEC. These findings suggest that the MMC-induced genotoxic stress in endothelial cells derived from different arteries is associated with differential secretion and gene expression of proinflammatory cytokines IL6 and IL8.

Co-Culture of Primary Human Coronary Artery and Internal Thoracic Artery Endothelial Cells Results in Mutually Beneficial Paracrine Interactions.

Although saphenous veins (SVs) are commonly used as conduits for coronary artery bypass grafting (CABG), internal thoracic artery (ITA) grafts have significantly higher long-term patency. As SVs and ITA endothelial cells (ECs) have a considerable level of heterogeneity, we suggested that synergistic paracrine interactions between CA and ITA ECs (HCAECs and HITAECs, respectively) may explain the increased resistance of ITA grafts and adjacent CAs to atherosclerosis and restenosis. In this study, we measured the gene and protein expression of the molecules responsible for endothelial homeostasis, pro-inflammatory response, and endothelial-to-mesenchymal transition in HCAECs co-cultured with either HITAECs or SV ECs (HSaVECs) for an ascending duration. Upon the co-culture, HCAECs and HITAECs showed augmented expression of endothelial nitric oxide synthase (eNOS) and reduced expression of endothelial-to-mesenchymal transition transcription factors Snail and Slug when compared to the HCAEC-HSaVEC model. HCAECs co-cultured with HITAECs demonstrated an upregulation of HES1, a master regulator of arterial specification, of which the expression was also exclusively induced in HSaVECs co-cultured with HCAECs, suggestive of their arterialisation. In addition, co-culture of HCAECs and HITAECs promoted the release of pro-angiogenic molecules. To conclude, co-culture of HCAECs and HITAECs results in reciprocal and beneficial paracrine interactions that might contribute to the better performance of ITA grafts upon CABG.

Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis.

Infective endocarditis (IE) is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1ß and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE.

A Genomics-Based Model for Prediction of Severe Bioprosthetic Mitral Valve Calcification.

Severe bioprosthetic mitral valve calcification is a significant problem in cardiovascular surgery. Unfortunately, clinical markers did not demonstrate efficacy in prediction of severe bioprosthetic mitral valve calcification. Here, we examined whether a genomics-based approach is efficient in predicting the risk of severe bioprosthetic mitral valve calcification. A total of 124 consecutive Russian patients who underwent mitral valve replacement surgery were recruited. We investigated the associations of the inherited variation in innate immunity, lipid metabolism and calcium metabolism genes with severe bioprosthetic mitral valve calcification. Genotyping was conducted utilizing the TaqMan assay. Eight gene polymorphisms were significantly associated with severe bioprosthetic mitral valve calcification and were therefore included into stepwise logistic regression which identified male gender, the T/T genotype of the rs3775073 polymorphism within the TLR6 gene, the C/T genotype of the rs2229238 polymorphism within the IL6R gene, and the A/A genotype of the rs10455872 polymorphism within the LPA gene as independent predictors of severe bioprosthetic mitral valve calcification. The developed genomics-based model had fair predictive value with area under the receiver operating characteristic (ROC) curve of 0.73. In conclusion, our genomics-based approach is efficient for the prediction of severe bioprosthetic mitral valve calcification.