Fibrosis markers and CRIM1 increase in chronic heart failure of increasing severity

Eleuteri, Ermanno; Stefano, Antonino Di; Vallese, Davide; Gnemmi, Isabella; Pitruzzella, Alessandro; Genta, Franco Tarro; Donne, Lorena Delle; Cappello, Francesco; Ricciardolo, Fabio Luigi Massimo; Giannuzzi, Pantaleo

doi:10.3109/1354750x.2014.896946

Cited by 5 publications

(3 citation statements)

References 44 publications

(50 reference statements)

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“…Similar to prior studies in patients with heart failure overall [31][32][33][34] , higher serum levels of IL6 or CRIM1 were associated with more severe forms of inflammatory cardiomyopathy in our study. Importantly, it had been shown previously that in IL6 deficient mice, prevalence and severity of myocarditis were reduced in the absence of IL6 31 .…”

Section: Discussionsupporting

confidence: 90%

Cytokines as Potential Novel Therapeutic Targets in Severe Inflammatory Cardiomyopathy

Suwalski,

Golpour,

Weiner

et al. 2023

Preprint

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Background: Despite currently available state-of-the art therapies, a substantial proportion of patients with inflammatory cardiomyopathy progresses to advanced heart failure. There is an urgent need for novel therapies to improve outcomes. We hypothesized that elevated cyto-kine levels in inflammatory cardiomyopathy may lead to cardiac injury and that specific cyto-kines are associated with severely decreased left ventricular function consequently, thereby suggesting their potential as therapeutic targets. Methods and Results: Blood samples collected from 529 patients at 2 registries were investi-gated. First, in a derivation cohort of inflammatory cardiomyopathy from our medical center (n=63), we discovered cytokines that correlate inversely with severely decreased left ventricu-lar ejection fraction (LVEF). We confirmed reproducibility of our results in an independent cohort from a national registry (n=425) and to some degree generalizability in a small cohort of idiopathic dilated cardiomyopathy (IDCM, n=41). In total, we identified 82 cytokines as-sociated with severely decreased LVEF (FDR < 0.05); a small portion had been previously proposed as therapeutic targets, while others emerged as novel discoveries. Finally, real-world data from electronic medical records further indicated the potential of inhibitors targeting cy-tokines of interest to confer a cardioprotective effect. Conclusions: We identified 82 cytokines associated with severe inflammatory cardiomyopa-thy. Our data were highly significant, reproducible, and generalizable to IDCM. The fact that some of the cytokines had been suggested as potential targets in prior literature supports valid-ity and plausibility of our data. Given that inhibition of cytokines is technically feasible, the identified proteins are compelling potential novel therapeutic targets.

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Section: Discussionsupporting

confidence: 90%

Cytokines as Potential Novel Therapeutic Targets in Severe Inflammatory Cardiomyopathy

Suwalski,

Golpour,

Weiner

et al. 2023

Preprint

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“…One study showed that statins decrease circulating fibrosis markers in patients with HF. 12 However, several factors can affect circulating fibrosis markers in patients with HF, including HF severity, 35 renal function, 36 and cardiac function. 17 Therefore, lower levels of circulating fibrosis markers in HF are hard to interpret.…”

Section: Discussionmentioning

confidence: 99%

Effects of 12 Weeks of Atorvastatin Therapy on Myocardial Fibrosis and Circulating Fibrosis Biomarkers in Statin-NaïVe Patients with Hypertension with Atherosclerosis

Chang

Lee

et al. 2016

Journal of Investigative Medicine

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“… 22 , 23 , 24 Interestingly, CRIM1 was documented to be expressed in coronary vascular smooth muscle cells and coronary endothelial cells during cardiac development 24 and serum levels of CRIM1 were reported to positively correlate with the severity of left ventricular failure in human. 25 SPON1 is a secreted and extracellular matrix‐attached protein of the thrombospondin family with obscure functions. Early work on this protein indicated that it stimulates vascular smooth muscle cell proliferation 26 and inhibits angiogenesis, 27 suggesting that increased plasma levels in patients with PAH may contribute to RV ischemia.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of Proteomics‐Discovered Circulating Inflammatory Biomarkers in Patients With Pulmonary Arterial Hypertension

Yokokawa,

Boucherat,

Martineau

et al. 2024

JAHA

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Background Pulmonary arterial hypertension (PAH) ultimately leads to right ventricular failure and premature death. The identification of circulating biomarkers with prognostic utility is considered a priority. As chronic inflammation is recognized as key pathogenic driver, we sought to identify inflammation‐related circulating proteins that add incremental value to current risk stratification models for long‐term survival in patients with PAH. Methods and Results Plasma levels of 384 inflammatory proteins were measured with the proximity extension assay technology in patients with PAH (n=60) and controls with normal hemodynamics (n=28). Among these, 51 analytes were significantly overexpressed in the plasma of patients with PAH compared with controls. Cox proportional hazard analyses and C‐statistics were performed to assess the prognostic value and the incremental prognostic value of differentially expressed proteins. A panel of 6 proteins (CRIM1 [cysteine rich transmembrane bone morphogenetic protein regulator 1], HGF [hepatocyte growth factor], FSTL3 [follistatin‐like 3], PLAUR [plasminogen activator, urokinase receptor], CLSTN2 [calsyntenin 2], SPON1 [spondin 1]) were independently associated with death/lung transplantation at the time of PAH diagnosis after adjustment for the 2015 European Society of Cardiology/European Respiratory Society guidelines, the REVEAL (Registry to Evaluate Early and Long‐Term PAH Disease Management) 2.0 risk scores, and the refined 4‐strata risk assessment. CRIM1, PLAUR, FSTL3, and SPON1 showed incremental prognostic value on top of the predictive models. As determined by Western blot, FSTL3 and SPON1 were significantly upregulated in the right ventricle of patients with PAH and animal models (monocrotaline‐injected and pulmonary artery banding‐subjected rats). Conclusions In addition to revealing new actors likely involved in cardiopulmonary remodeling in PAH, our screening identified promising circulating biomarkers to improve risk prediction in PAH, which should be externally confirmed.

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Fibrosis markers and CRIM1 increase in chronic heart failure of increasing severity

Cited by 5 publications

References 44 publications

Cytokines as Potential Novel Therapeutic Targets in Severe Inflammatory Cardiomyopathy

Cytokines as Potential Novel Therapeutic Targets in Severe Inflammatory Cardiomyopathy

Effects of 12 Weeks of Atorvastatin Therapy on Myocardial Fibrosis and Circulating Fibrosis Biomarkers in Statin-NaïVe Patients with Hypertension with Atherosclerosis

Prognostic Significance of Proteomics‐Discovered Circulating Inflammatory Biomarkers in Patients With Pulmonary Arterial Hypertension

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