Low Plasma Carnosinase-1 Activity in Patients with Left Ventricular Systolic Dysfunction: Implications for Carnosine Therapy in Heart Failure

I-Chau Liang; Ettore Gilardoni; Islam A. Berdaweel; Knute D. Carter; Ethan J. Anderson

doi:10.3390/ijms26062608

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Low Plasma Carnosinase-1 Activity in Patients with Left Ventricular Systolic Dysfunction: Implications for Carnosine Therapy in Heart Failure

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Low Plasma Carnosinase-1 Activity in Patients with Left Ventricular Systolic Dysfunction: Implications for Carnosine Therapy in Heart Failure

I-Chau Liang, Ettore Gilardoni, Islam A. Berdaweel, Knute D. Carter and Ethan J. Anderson

International journal of molecular sciences, Vol.26(6), 2608

03/14/2025

DOI: 10.3390/ijms26062608

PMCID: PMC11942450

PMID: 40141250

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Abstract

Therapeutic efficacy of histidyl dipeptides such as carnosine is hampered by circulating carnosinase-1 (CN1), which catalyzes carnosine’s hydrolysis and degradation. Prior reports suggest that oral carnosine may improve cardiometabolic parameters in patients with heart failure (HF), but whether CN1 activity is affected by HF is unknown. Here, we measured CN1 content and carnosine degradation rate (CDR) in preoperative plasma samples from a cohort of patients (n = 138) undergoing elective cardiac surgery to determine whether plasma CN1 and/or CDR varied with left ventricular (LV) systolic dysfunction. CN1 content was normally distributed in the cohort, but plasma CDR displayed a quasi-bimodal distribution into high- (>2 nmol/(h*μL)) and low-activity (≤2 nmol/(h*μL)) clusters. Multivariable analysis confirmed female sex, diabetes and LV systolic dysfunction was associated with the low-activity CDR cluster. Although CN1 content did not differ, logistic regression analysis revealed that CDR and CN1-specific activity (CDR/CN1 content) was significantly lower in patients with both moderate (ejection fraction, EF ≥ 35 to <50%) and severe LV systolic dysfunction (EF < 35%) compared with patients in the normal range (EF ≥ 50%). These findings suggest that plasma CN1 activity is regulated by factors independent of expression, and that a decline in LV systolic function is associated with low CN1 activity. Further studies are needed to delineate specific mechanisms controlling CN1 expression and activity, which will facilitate the development of carnosine and other histidyl dipeptide therapies for cardiometabolic disorders such as HF.

carnosinase

CNDP1

CN1 protein

carnosine

heart failure

Details

Title: Subtitle: Low Plasma Carnosinase-1 Activity in Patients with Left Ventricular Systolic Dysfunction: Implications for Carnosine Therapy in Heart Failure
Creators: I-Chau Liang - University of Iowa
Ettore Gilardoni - University of Iowa
Islam A. Berdaweel - University of Iowa
Knute D. Carter - University of Iowa
Ethan J. Anderson - University of Iowa
Resource Type: Journal article
Publication Details: International journal of molecular sciences, Vol.26(6), 2608
DOI: 10.3390/ijms26062608
PMID: 40141250
PMCID: PMC11942450
NLM abbreviation: Int J Mol Sci
ISSN: 1422-0067
eISSN: 1422-0067
Publisher: MDPI
Grant note: American Heart Association: 20SFRN35200003 American Heart Association's Strategically Focused Research Network: R01HL122863, R01HL167087 National Institutes of Health
This project was supported by funding from the American Heart Association's Strategically Focused Research Network award 20SFRN35200003 and National Institutes of Health grants R01HL122863 and R01HL167087 to EJA.
Language: English
Date published: 03/14/2025
Academic Unit: Pharmaceutical Sciences and Experimental Therapeutics; Biostatistics; Fraternal Order of Eagles Diabetes Research Center
Record Identifier: 9984801841002771

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