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Procollagen C-Proteinase Enhancer 1 (PCPE-1) is a marker of myocardial fibrosis and impaired cardiac function in a murine model of pressure overload

Abstract : Aims Procollagen C-proteinase enhancer 1 (PCPE-1) is an extracellular matrix protein and a major regulator of fibrillar collagen biosynthesis. Previous work has shown that its abundance is often increased in the context of tissue repair and fibrosis. The present study was designed to evaluate its potential as a biomarker of myocardial interstitial fibrosis (MIF), a well-established pathogenic pathway leading to heart failure. (2) Methods and Results Cardiac fibrosis was induced in rats using an optimized model of chronic pressure overload triggered by angiotensin II and N ω -nitro-L-arginine methyl ester (L-NAME). All treated animals suffered from heart hypertrophy and the increase in heart collagen volume fraction (CVF), evidenced by histology and 68 Ga-Collagelin uptake, confirmed the development of cardiac fibrosis. Functional analysis by simultaneous PET-MRI further showed that our model closely reflected the pathological features seen in human MIF, including left ventricle thickening and diastolic dysfunction associated with decreased ejection fraction. PCPE-1 mRNA and protein levels were augmented by factors of 3.4 and 6.1 respectively in the heart tissue of treated rats. Moreover, protein abundance was well-correlated with CVF (r=0.92, p<0.0001) and PCPE-1 immuno-detection mainly localized the protein to fibrotic areas. Finally, PCPE-1 plasma levels measured by ELISA were increased in fibrotic rats compared to controls. (3) Conclusion Together, our findings demonstrate that PCPE-1 levels in the heart and circulation tightly reflect the cardiac fibrosis status and heart function impairment in rats and suggest that it could be a very useful marker to monitor human heart diseases leading to fibrosis.
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Preprints, Working Papers, ...
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https://hal.archives-ouvertes.fr/hal-03372769
Contributor : Sandrine Vadon - Le Goff Connect in order to contact the contributor
Submitted on : Monday, October 11, 2021 - 10:10:22 AM
Last modification on : Tuesday, January 4, 2022 - 6:48:02 AM
Long-term archiving on: : Wednesday, January 12, 2022 - 7:07:59 PM

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Priscillia Lagoutte, Alexandra Oudot, Mélissa Dussoyer, Victor Goncalves, Mélanie Guillemin, et al.. Procollagen C-Proteinase Enhancer 1 (PCPE-1) is a marker of myocardial fibrosis and impaired cardiac function in a murine model of pressure overload. 2021. ⟨hal-03372769⟩

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