Association of irisin levels with cardiac magnetic resonance, inflammatory, and biochemical parameters in patients with chronic heart failure versus controls.

BACKGROUND AND AIMS: Chronic heart failure (CHF) represents a significant cause of morbidity and mortality globally. Metabolic maladaptation has proven to be critical in the progression of this condition. Preclinical studies have shown that irisin, an adipomyokine involved in metabolic regulations, can induce positive cardioprotective effects by improving cardiac remodeling, cardiomyocyte viability, calcium delivery, and reducing inflammatory mediators. However, data on clinical studies identifying the associations between irisin levels and functional imaging parameters are scarce in CHF patients. The objective of this study was to determine the association of irisin levels with cardiac imaging measurements through cardiac magnetic resonance, inflammatory markers, and biochemical parameters in patients with CHF compared with control subjects. METHODS AND RESULTS: Thirty-two subjects diagnosed with CHF and thirty-two healthy controls were evaluated in a cross-sectional study. Serum irisin levels were significantly lower in patients with CHF than in controls. This is the first study to report a significant positive correlation between irisin levels and cardiac magnetic resonance parameters such as left ventricular ejection fraction, fraction shortening, and global radial strain. A negative correlation was demonstrated between irisin levels and brain natriuretic peptide, insulin levels, and Homeostatic model assessment for insulin resistance index. We did not observe significant correlations between irisin levels and inflammatory cytokines. CONCLUSIONS: Given the importance of fraction shortening and global radial strain as accurate markers of ventricular wall motion, these results support the hypothesis that irisin may play an essential role in maintaining an adequate myocardial wall architecture, deformation, and thickness.

Serum Irisin Levels, Endothelial Dysfunction, and Inflammation in Pediatric Patients with Type 2 Diabetes Mellitus and Metabolic Syndrome.

The prevalence of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) has increased in the pediatric population. Irisin, an adipomyokine, is involved in white adipose tissue browning, energy expenditure, insulin sensitivity, and anti-inflammatory pathways. Data on the associations among circulating irisin levels, soluble cell adhesion molecules (sCAMs), and inflammatory cytokines is scarce in children and adolescents with MetS and T2DM. Subjects aged 6-16 years were grouped into T2DM, MetS, and healthy controls. Serum irisin levels were significantly lower in the MetS (6.6 [2.8-18.0] ng/mL) and T2DM (6.8 [2.2-23.2] ng/mL) groups compared with controls (30.3 [24.6-57.1] ng/mL). Negative correlations between irisin and the BMI percentile (R = -0.358), WC percentile (R = -0.308), and triglycerides (R = -0.284) were identified, while positive associations with TC (R = 0.287), HDL-c (R = 0.488), and LDL-c (R = 0.414) were observed. Significant negative correlations were found between irisin and sNCAM (R = -0.382), sICAM-2 (R = -0.300), sVCAM-1 (R = -0.292), MCP-1 (R = -0.308), and IFN-α2 (R = -0.406). Of note, lower concentrations of most sCAMs (sICAM-1, sPSGL-1, sP-selectin, sEpCAM, sICAM-2, sALCAM, sPECAM-1, sCD44, sVCAM-1, sICAM-3, sL-selectin, and sNCAM) were shown in T2DM subjects compared with MetS patients. Lower irisin levels induce a lack of inhibition of oxidative stress and inflammation. In T2DM, higher ROS, AGEs, glucotoxicity, and inflammation trigger endothelial cell apoptosis, which downregulates the sCAM expression as a compensatory mechanism to prevent further vascular damage. In opposition, in subjects with MetS that have not yet developed T2DM and its accompanying stressors, the upregulation of the sCAM expression is ensued.

Correlation of Vitamin D with Inflammatory Cytokines, Atherosclerotic Parameters, and Lifestyle Factors in the Setting of Heart Failure: A 12-Month Follow-Up Study.

Vitamin D deficiency is highly prevalent worldwide. It has been associated with heart failure (HF) given its immunoregulatory functions. In-vitro and animal models have shown protective roles through mechanisms involving procollagen-1, JNK2, calcineurin/NFAT, NF-κB, MAPK, Th1, Th2, Th17, cytokines, cholesterol-efflux, oxLDL, and GLUT4, among others. A 12-month follow-up in HF patients showed a high prevalence of vitamin D deficiency, with no seasonal variation (64.7-82.4%). A positive correlation between serum 25(OH)D concentration and dietary intake of vitamin D-rich foods was found. A significant inverse correlation with IL-1ß (R = -0.78), TNF-α (R = -0.53), IL-6 (R = -0.42), IL-8 (R = -0.41), IL-17A (R = -0.31), LDL-cholesterol (R = -0.51), Apo-B (R = -0.57), total-cholesterol (R = -0.48), and triglycerides (R = -0.32) was shown. Cluster analysis demonstrated that patients from cluster three, with the lowest 25(OH)D levels, presented the lowermost vitamin D intake, IL-10 (1.0 ± 0.9 pg/mL), and IL-12p70 (0.5 ± 0.4 pg/mL), but the highest TNF-α (9.1 ± 3.5 pg/mL), IL-8 (55.6 ± 117.1 pg/mL), IL-17A (3.5 ± 2.0 pg/mL), total-cholesterol (193.9 ± 61.4 mg/dL), LDL-cholesterol (127.7 ± 58.2 mg/dL), and Apo-B (101.4 ± 33.4 mg/dL) levels, compared with patients from cluster one. Although the role of vitamin D in the pathogenesis of HF in humans is still uncertain, we applied the molecular mechanisms of in-vitro and animal models to explain our findings. Vitamin D deficiency might contribute to inflammation, remodeling, fibrosis, and atherosclerosis in patients with HF.