Interleukin-22 regulating fibrosis on mouse cardiac fibroblasts through STAT3 signaling pathway

Objective:To observe the effects of interleukin-22(IL-22)on the expression of type Ⅲ collagen,cytokines,growth factors and chemokines in mouse cardiac fibroblasts in vitro.Methods:Mouse cardiac fibroblasts were treated with0μg/L(control),1μg/L(low concentration)and 100μg/L(high concentration)IL-22,respectively.In addition,cells treated with 100μmol/L static(an STAT3 pathway inhibitor)and 100μg/L IL-22 was defined as the block group.After treatment for 48 hours,the mRNA level of collagen type Ⅲ A1(Col3-A1),matrix metalloproteinase-1(Timp-1),IL-22receptor(IL-22R),interleukin 10-related T cellderived inducible factor beta(Iltifb),fibroblast growth factor1(Fgf1)and C-C motif chemokine ligand 4(Ccl4)were determined by RT-PCR.The expression of Col3-A1 in cardiac fibroblasts was also semi-quantified by immunofluorescence.Results:Expression of Col3-A1 decreased in the low and high concentration groups,but significantly increased in the block group(all P <0.05).The expression of Timp-1increased in the low,high concentration and block groups compared with that in the control group,but it was significantly lower in the high concentration group than that in the low concentration group(P <0.05).The expression of IL-22 Rand Iltifb was significantly increased in the low,high concentration and block groups compared with that in the control group(P <0.05),but there was no statistical difference between the high concentration group and block group.The expression of Fgf1 and Ccl4 was significantly decreased in the low,high concentration and block groups compared with that in the control group(P <0.05),but there was no statistic difference between the high concentration group and block group as well.Conclusion:IL-22 effected on the expression of Col3-A1 and Timp-1,which was possibly through the JAK-STAT3 signaling pathway in mice cardiac fibroblasts.

Prevalence, risk factors, and survival associated with pulmonary hypertension and heart failure among patients with underlying coronary artery disease: a national prospective, multicenter registry study in China

Background: Coronary artery disease (CAD) is the commonest cause of heart failure (HF), whereas pulmonary hypertension (PH) has not been established or reported in this patient population. Therefore, we assessed the prevalence, risk factors, and survival in CAD-associated HF (CAD-HF) complicated with PH.Methods: Symptomatic CAD-HF patients were continuously enrolled in this prospective, multicenter registry study. Echocardiography, coronary arteriography, left and right heart catheterization (RHC), and other baseline clinical data were recorded. Patients were followed up and their survival was recorded.Results: One hundred and eighty-two CAD-HF patients were enrolled, including 142 with HF with a preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF];left ventricular ejection fraction [LVEF] ≥50%) and 40 with a reduced ejection fraction (heart failure with reduced ejection fraction [HFrEF];LVEF < 50%). PH was diagnosed with RHC in 77.5% of patients. Patients with PH showed worse hemodynamic parameters and higher mortality. HFrEF-PH patients had worse survival than HFpEF-PH patients. CAD-HF patients with an enlarged left ventricular end-diastolic diameter and reduced hemoglobin were at higher risk of PH. Nitrate treatment reduced the risk of PH. Elevated creatinine and mean pulmonary arterial pressure (mPAP), diastolic pressure gradient (DPG) ≥7 mmHg, and previous myocardial infarction (MI) entailed a higher risk of mortality in CAD-HF patients with PH.Conclusions: PH is common in CAD-HF and worsens the hemodynamics and survival in these patients. Left ventricle enlargement and anemia increase the risk of PH in CAD-HF. Patients may benefit from nitrate medications. Renal impairment, elevated mPAP, DPG ≥7 mmHg, and previous MI are strong predictors of mortality in CAD-HF-PH patients.Trial Registration: ClinicalTrials.gov, NCT02164526.