leptin and Rupture--Spontaneous

Vitamin D is a fat soluble vitamin involved in calcium and bone metabolism; recently its deficiency has been related to cardiovascular disease. In cardiac tissue, vitamin D suppresses metalloproteinases (MMPs) expression, enzymes directly associated with vulnerable plaque.. To investigate whether the association between vitamin D and leptin is related to markers of vulnerable plaque, such as MMPs in patients with acute myocardial infarction.. We studied 66 male patients with acute myocardial infarction, undergoing primary angioplasty. Blood samples were obtained at admission and 24hs after the surgery. Leptin and vitamin D concentrations in serum and MMP-2 and -9 activities in plasma were determined.. MMP-2 activity was increased in Vitamin D deficient/insufficient patients at admission (p=0.04) and 24 hs later (p=0.05). In a linear regression model, vitamin D explained 24% of the variance of MMP-2 activity (F=2.839 p=0.04). At admission, vitamin D correlated with serum leptin (r=-0.302 p=0.033), and explained 39.5% of its variation (F=4.432 p=0.003).. In the studied population, vitamin D was inversely related to MMP-2 and leptin which are involved in coronary artery disease and acute myocardial infarction. The decrease in this hormone levels would be associated with a worse metabolic profile in acute coronary syndrome patients.

Topics: Adult; Aged; Biomarkers; Coronary Artery Disease; Humans; Leptin; Male; Matrix Metalloproteinase 2; Middle Aged; Plaque, Atherosclerotic; Rupture, Spontaneous; ST Elevation Myocardial Infarction; Time Factors; Vitamin D; Vitamin D Deficiency

The rupture of unstable carotid atherosclerotic plaques is one of the main causes of cerebrovascular ischemic events. There is need for circulating markers that can predict plaque instability and risk of stroke. Proinflammatory chemerin, leptin, and resistin, along with anti-inflammatory adiponectin, are adipokines with direct influence on vascular function. We investigated the association of circulating adipokines with carotid plaque instability and cerebrovascular symptomatology.. Neurologically symptomatic and asymptomatic patients (n=165) scheduled for carotid endarterectomy were recruited. Fasting blood samples were collected preoperatively; adiponectin and leptin levels were determined by radioimmunoassay; and chemerin and resistin levels were measured by enzyme-linked immunosorbent assays. The instability of plaque specimens was assessed using gold-standard histological classifications. Chemerin was significantly associated with plaque instability. The fully adjusted model, accounting for age, sex, body mass index, high-sensitivity C-reactive protein, type 2 diabetes mellitus, and circulating adiponectin, leptin, and resistin, yielded an odds ratio of 0.991 (95% confidence interval 0.985-0.998) for plaque instability per unit increase in chemerin. High leptin levels were significantly associated with presence of specific features of plaque instability. In subjects with type 2 diabetes mellitus, resistin levels were significantly elevated in symptomatic when compared with asymptomatic subjects (P=0.001) and increased the risk of cerebrovascular symptomatology (adjusted odds ratio 1.264, 95% confidence interval 1.004-1.594).. Low chemerin and high resistin levels were associated with carotid disease severity, suggesting that these adipokines may act as potential markers for plaque instability and stroke risk. Future studies are needed to assess causation between circulating adipokines and plaque instability.

Topics: Adiponectin; Aged; Biomarkers; Carotid Stenosis; Cerebrovascular Disorders; Chemokines; Chi-Square Distribution; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Plaque, Atherosclerotic; Predictive Value of Tests; Prognosis; Resistin; Risk Assessment; Risk Factors; Rupture, Spontaneous; Severity of Illness Index

Resident macrophages play an important role in atheromatous plaque rupture. The macrophage gene expression signature associated with plaque rupture is incompletely defined due to the complex cellular heterogeneity in the plaque. We aimed to characterise differential gene expression in resident plaque macrophages from ruptured and stable human atheromatous lesions.. We performed genome-wide expression analyses of isolated macrophage-rich regions of stable and ruptured human atherosclerotic plaques. Plaques present in carotid endarterectomy specimens were designated as stable or ruptured using clinical, radiological and histopathological criteria. Macrophage-rich regions were excised from 5 ruptured and 6 stable plaques by laser micro-dissection. Transcriptional profiling was performed using Affymetrix microarrays. The profiles were characteristic of activated macrophages. At a false discovery rate of 10%, 914 genes were differentially expressed between stable and ruptured plaques. The findings were confirmed in fourteen further stable and ruptured samples for a subset of eleven genes with the highest expression differences (p < 0.05). Pathway analysis revealed that components of the PPAR/Adipocytokine signaling pathway were the most significantly upregulated in ruptured compared to stable plaques (p = 5.4 × 10(-7)). Two key components of the pathway, fatty-acid binding-protein 4 (FABP4) and leptin, showed nine-fold (p = 0.0086) and five-fold (p = 0.0012) greater expression respectively in macrophages from ruptured plaques.. We found differences in gene expression signatures between macrophages isolated from stable and ruptured human atheromatous plaques. Our findings indicate the involvement of FABP4 and leptin in the progression of atherosclerosis and plaque rupture, and suggest that down-regulation of PPAR/adipocytokine signaling within plaques may have therapeutic potential.

Topics: Aged; Fatty Acid-Binding Proteins; Female; Gene Expression Regulation; Genome-Wide Association Study; Humans; Leptin; Macrophages; Male; Plaque, Atherosclerotic; Rupture, Spontaneous

A multifactorial aetiology of coronary artery disease (CAD) has been established in the recent past. Extensive research is now underway to understand the mechanisms responsible for plaque vulnerability. The identification of a novel biomarker that will help in the assessment of plaque status is urgently needed for the purpose of patient stratification and prognostication. The aim of the present study was to evaluate leptin, pregnancy-associated plasma protein A (PAPP-A) and C-reactive protein (CRP) levels in patients with acute coronary syndrome and to assess their diagnostic efficacy in the identification of vulnerable plaques.. The study group comprised 105 patients who had chest pain along with ECG changes (ST elevation, ST depression, T inversion) and raised cardiac enzyme levels. Sixty-two patients with chest pain and ECG changes but with normal cardiac enzyme profiles were included in the control group. Lipid profiles, and leptin, PAPP-A and CRP levels were assessed in these two groups. Receiver operating characteristics (ROC) curves were plotted to determine the utility of the parameters under study as markers of plaque vulnerability.. Significantly higher levels of serum lipoprotein (a), leptin, PAPP-A and high-sensitivity CRP (hs-CRP) were observed in the cases than in the controls. A positive correlation was observed between CRP and PAPP-A levels as well as CRP and leptin concentrations. ROC curve analysis revealed similar efficacies of CRP and PAPP-A levels in their ability to detect unstable plaques with areas under the curve of 0.762 and 0.732, respectively. Multivariate analysis established the superiority of hs-CRP as a predictor of plaque instability.. Our study highlights the utility of both CRP and PAPP-A levels as determinants of plaque instability. Our findings necessitate population-based follow-up studies to establish the superiority of either of the two biomarkers in the field of preventive cardiology.

Topics: Acute Coronary Syndrome; Adult; Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Coronary Vessels; Disease Progression; Electrocardiography; Female; Humans; India; Inflammation Mediators; Leptin; Lipoprotein(a); Male; Middle Aged; Multivariate Analysis; Plaque, Atherosclerotic; Predictive Value of Tests; Pregnancy-Associated Plasma Protein-A; Risk Assessment; Risk Factors; Rupture, Spontaneous

The purpose of this study was to identify whether leptin and connective tissue growth factor (CTGF) occur in the degenerative fibrocartilage disk and whether cartilage cells express leptin receptors.. The study included 23 patients diagnosed with degenerative articular disk tears of the triangular fibrocartilage (TFC) (Palmer type 2C). Patients were divided into 2 groups based on ulna length: 1 group consisted of patients with an ulna-positive variance (group A), and the other group included patients with ulna-negative or -neutral variance (group B). After arthroscopic debridement of the TFC, histologic sections of biopsy specimens were prepared. The biopsy specimens were immunohistochemically analyzed, and the quantity of leptin-, CTGF-, and leptin receptor-positive cells was assessed.. Cells positive for leptin, leptin receptor, and CTGF were found. The number of cells positive for leptin was significantly increased in specimens of patients with an ulna-negative variance (group B). In contrast, no significant difference was found for leptin receptor and CTGF in biopsy specimens of patients with ulna-positive or ulna-negative/neutral variance. The inner, middle, and outer zones of the disk do not express significantly different quantities of marker-positive cells.. Degenerative fibrocartilage disk tissue cells exhibit leptin receptors and are exposed to the markers leptin and CTGF, providing evidence of a local paracrine system and regenerative processes. Cells of disks from patients with an ulna-neutral/negative length express significantly higher numbers of leptin-positive cells.. Level II, diagnostic study.

Topics: Adult; Biomarkers; Biopsy; Cartilage, Articular; Cells, Cultured; Chondrocytes; Connective Tissue Growth Factor; Debridement; Female; Humans; Immunohistochemistry; Joint Diseases; Leptin; Male; Prognosis; Receptors, Leptin; Rupture, Spontaneous; Severity of Illness Index; Wrist Joint