Decreased circulating catestatin levels are associated with coronary artery disease: The emerging anti-inflammatory role

Chen, Yanjia; Wang, Xiaoqun; Yang, Chi; Su, Xiuxiu; Yang, Wenbo; Dai, Yang; Han, Hui; Jiang, Jie; Lü, Lin; Wang, Haibo; Chen, Qiujing; Jin, Wei

doi:10.1016/j.atherosclerosis.2018.12.025

Cited by 36 publications

(32 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because the processing of CgA to CST is compromised in several diseases [40][41][42][43][44] , we determined plasma CgA and CST levels in patients with Crohn's disease and with ulcerative colitis, both with active disease and in remission ( Fig. 1E; Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Chromogranin A regulates gut permeabilityviathe antagonistic actions of its proteolytic peptides

Muntjewerff

Tang

Lutter

et al. 2020

Preprint

View full text Add to dashboard Cite

Background and AimsA ‘leaky’ gut barrier has been implicated in the initiation and progression of a multitude of diseases, e.g., inflammatory bowel disease, irritable bowel syndrome, celiac disease, and colorectal cancers. Here we asked how Chromogranin A (CgA), a major hormone produced by the enteroendocrine cells, and Catestatin (CST), the most abundant CgA-derived proteolytic peptide, affect the gut barrier.Methods and ResultsUltrastructural studies on the colons from Catestatin (CST: hCgA352-372) knockout (CST-KO) mice revealed (i) altered morphology of tight (TJ) and adherens (AJ) junctions and desmosomes, indicative of junctional stress and (ii) an increased infiltration of immune cells compared to controls. Flow cytometry studies confirmed these cells to be macrophages and CD4+ T cells. Gene expression studies confirmed that multiple TJ-markers were reduced, with concomitant compensatory elevation of AJ and desmosome markers. Consistently, the levels of plasma FITC-dextran were elevated in the CST-KO mice, confirming leakiness’ of the gut. Leaky gut in CST-KO mice correlated with inflammation and a higher ratio of Firmicutes to Bacteroidetes, a dysbiotic pattern commonly encountered in a multitude of diseases. Supplementation of CST-KO mice with recombinant CST reversed this leakiness and key phenotypes. Supplementation of CgA-KO mice with either CST alone, or with the pro-inflammatory proteolytic CgA fragment pancreastatin (PST: CgA250-301) showed that gut permeability is regulated by the antagonistic roles of these two peptide hormones: CST reduces and PST increases leakiness.ConclusionWe conclude that the enteroendocrine cell-derived hormone, CgA regulates gut permeability. CST is both necessary and sufficient to reduce the leakiness. CST acts primarily via antagonizing the effects of PST.What you need to knowBackground and ContextThe intestinal barrier is disrupted in many intestinal diseases such as Crohn’s disease. Chromogranin A (CgA) is produced by enteroendocrine cells in the gut. CgA is proteolytically cleaved into bioactive peptides including catestatin (CST) and pancreastatin (PST). The role of CgA in the gut is unknown.New findingsCgA is efficiently processed to CST in the gut and this processing might be decreased during active Crohn’s disease. CST promotes epithelial barrier function and reduces inflammation by counteracting PST.LimitationsThe complete mechanism of intestinal barrier regulation by CST likely involves a complex interplay between the enteroendocrine system, metabolism, the epithelium, the immune system and the gut microbiota.ImpactOur findings indicate that CST is a key modulator of the intestinal barrier and immune functions that correlates with disease severity of Crohn’s disease. CST could be a target for therapeutic interventions in Crohn’s disease.

show abstract

Section: Resultsmentioning

confidence: 99%

Chromogranin A regulates gut permeabilityviathe antagonistic actions of its proteolytic peptides

Muntjewerff

Tang

Lutter

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Since the physiological effects of norepinephrine and SNS mediators promote tachyphylaxis and systemic vasoconstriction it is possible that these effects contributed to detrimental vascular remodeling as evident in increased arterial stiffness parameters. Finally, although CST stand-alone generally confers protective effects on heart and vasculature, as shown in a handful of previous studies [22,23,60,61], it is possible that in the setting of IBD, a disease state characterized by persistent inflammation and increased SNS activity, effects of CST, despite being elevated in circulation, are not sufficient to compensate for adverse arterial remodeling that is propagated by the proinflammatory and adrenergic cellular pathways. However, due to a substantial evidence gap in this regard and lack of studies reporting on CST and arterial stiffness parameters, these hypothetical interactions need to be confirmed in future preclinical and mechanistic studies.…”

Section: Discussionmentioning

confidence: 97%

Serum Catestatin Levels and Arterial Stiffness Parameters Are Increased in Patients with Inflammatory Bowel Disease

Živković

Matetić

Hadjina

et al. 2020

JCM

View full text Add to dashboard Cite

Catestatin (CST) is an important peptide in the pathophysiology of chronic inflammatory disorders. However, clinical studies on inflammatory bowel disease (IBD) patients are lacking. Our goal was to investigate CST concentrations in IBD patients compared to healthy subjects. Additionally, we aimed to determine arterial stiffness parameters in relation to CST. This cross-sectional study compared 80 IBD patients (45 Crohn’s disease (CD) and 35 ulcerative colitis (UC) patients) with 75 control subjects. Serum CST levels were significantly higher in the IBD group compared to control subjects (11.29 ± 9.14 vs. 7.13 ± 6.08 ng/mL, p = 0.001) and in the UC group compared to CD patients (13.50 ± 9.58 vs. 9.03 ± 6.92 ng/mL, p = 0.021), irrespective of age and BMI. IBD patients exhibited significantly higher values of heart rate adjusted central augmentation index (cAIx-75) (14.88 ± 10.59 vs. 6.87 ± 9.50 %, p < 0.001) and pulse wave velocity (PWV) (8.06 ± 3.23 vs. 6.42 ± 1.47 m/s, p < 0.001) compared to control group. Furthermore, PWV was the only significant independent correlate of CST (B = 1.20, t = 4.15, p < 0.001), while CST, PWV, cAIx-75, high-sensitivity C-reactive protein and BMI were significant predictors of positive IBD status (1.089 (1.022–1.161), 1.515 (1.166–1.968), 1.060 (1.024–1.097), 1.458 (1.116–1.906), 0.793 (0.683–0.920), respectively). Serum CST levels were significantly higher in IBD patients compared to controls and an independent positive correlation of CST with PWV existed. Therefore, it is possible that CST could have a role in the complex pathophysiology of IBD and its cardiovascular complications.

show abstract

“…In a study among untreated hypertensive patients, catestatin levels correlated positively with HDL-cholesterol levels but no associations were observed with respect to the total cholesterol or other cholesterol fractions [50], while CST correlated negatively with HDL cholesterol among obstructive sleep apnea patients [11]. Similarly, catestatin significantly retarded aortic atherosclerotic lesions with declined lipoprotein-induced foam cell formation in a preclinical experiment [51], while its levels were inversely associated with the severity of atherosclerosis, among patients with CAD [52]. These data suggest that CST is associated with an improved lipid profile and likely exerts antiatherosclerotic effects, thus, partially explaining the negative associations of LDL and non-HDL cholesterol fractions with the CST levels, as observed in this study.…”

Section: Discussionmentioning

confidence: 99%

Catestatin in Acutely Decompensated Heart Failure Patients: Insights from the CATSTAT-HF Study

Borovac

Glavaš

Grabovac

et al. 2019

JCM

View full text Add to dashboard Cite

The role of catestatin (CST) in acutely decompensated heart failure (ADHF) and myocardial infarction (MI) is poorly elucidated. Due to the implicated role of CST in the regulation of neurohumoral activity, the goals of the study were to determine CST serum levels among ninety consecutively enrolled ADHF patients, with respect to the MI history and left ventricular ejection fraction (LVEF) and to examine its association with clinical, echocardiographic, and laboratory parameters. CST levels were higher among ADHF patients with MI history, compared to those without (8.94 ± 6.39 vs. 4.90 ± 2.74 ng/mL, p = 0.001). CST serum levels did not differ among patients with reduced, midrange, and preserved LVEF (7.74 ± 5.64 vs. 5.75 ± 4.19 vs. 5.35 ± 2.77 ng/mL, p = 0.143, respectively). In the multivariable linear regression analysis, CST independently correlated with the NYHA class (β = 0.491, p < 0.001), waist-to-hip ratio (WHR) (β = −0.237, p = 0.026), HbA1c (β = −0.235, p = 0.027), LDL (β = −0.231, p = 0.029), non-HDL cholesterol (β = −0.237, p = 0.026), hs-cTnI (β = −0.221, p = 0.030), and the admission and resting heart rate (β = −0.201, p = 0.036 and β = −0.242, p = 0.030), and was in positive association with most echocardiographic parameters. In conclusion, CST levels were increased in ADHF patients with MI and were overall associated with a favorable cardiometabolic profile but at the same time reflected advanced symptomatic burden (CATSTAT-HF ClinicalTrials.gov number, NCT03389386).

show abstract

Decreased circulating catestatin levels are associated with coronary artery disease: The emerging anti-inflammatory role

Cited by 36 publications

References 42 publications

Chromogranin A regulates gut permeabilityviathe antagonistic actions of its proteolytic peptides

Chromogranin A regulates gut permeabilityviathe antagonistic actions of its proteolytic peptides

Serum Catestatin Levels and Arterial Stiffness Parameters Are Increased in Patients with Inflammatory Bowel Disease

Catestatin in Acutely Decompensated Heart Failure Patients: Insights from the CATSTAT-HF Study

Contact Info

Product

Resources

About