Circulating MiR-30b-5p is upregulated in Cavalier King Charles Spaniels affected by early myxomatous mitral valve disease

Abstract

There is a growing interest in developing new molecular markers of heart disease in young dogs affected by myxomatous mitral valve disease. The study aimed to measure 3 circulating microRNAs and their application as potential biomarkers in the plasma of Cavalier King Charles Spaniels with early asymptomatic myxomatous mitral valve disease. The hypothesis is that healthy Cavalier King Charles Spaniels have different microRNA expression profiles than affected dogs in American College of Veterinary Internal Medicine (ACVIM) stage B1. The profiles can differ within the same class among subjects of different ages. This is a prospective cross-sectional study. Thirty-three Cavalier King Charles Spaniels in ACVIM stage B1 were divided into three groups (11 younger than 3 years, 11 older than 3 years and younger than 7 years, and 11 older than 7 years), and 11 healthy (ACVIM stage A) dogs of the same breed were included as the control group. Three circulating microRNAs (miR-1-3p, miR30b-5p, and miR-128-3p) were measured by quantitative real-time PCR using TaqMan® probes. Diagnostic performance was evaluated by calculating the area under the receiver operating curve (AUC). MiR-30b-5p was significantly higher in ACVIM B1 dogs than in ACVIM A subjects, and the area under the receiver operating curve was 0.79. According to the age of dogs, the amount of miR-30b-5p was statistically significantly higher in group B1<3y (2.3 folds, P = 0.034), B1 3-7y (2.2 folds, P = 0.028), and B1>7y (2.7 folds, P = 0.018) than in group A. The area under the receiver operating curves were fair in discriminating between group B1<3y and group A (AUC 0.780), between B1 3-7y and A (AUC 0.78), and good in discriminating between group B1>7y and A (AUC 0.822). Identifying dogs with early asymptomatic myxomatous mitral valve disease through the evaluation of miR-30b-5p represents an intriguing possibility that certainly merits further research. Studies enrolling a larger number of dogs with preclinical stages of myxomatous mitral valve disease are needed to expand further and validate conclusively the preliminary findings from this report.

Preliminary prospective study on the predictive significance of plasma miR-30b-5p through the study of echocardiographic modifications in Cavalier King Charles Spaniels affected by different stages of myxomatous mitral valve disease: the PRIME study

“…A study published by Bagardi et al [7] conducted on the CKCS recently provided interesting results for miR-30b-5p in ACVIM class B1 CKCSs, demonstrating that miR-30b-5p can discriminate between B1 subjects and healthy dogs, and B1 CKCSs younger than 3 years of age and healthy dogs [7]. Since a heart murmur is uncommon to detect in young patients and echocardiographic changes can be misclassified as normal findings by inexperienced sonographers, miR-30b-5p can support the early diagnosis of MMVD-affected dogs [32].…”

“…Thus, the need arises to create studies that are statistically and methodologically more robust. To achieve this, the present work tries to assess the predictive value of one of the most promising of the miRNAs investigated to date [7], namely miR-30b-5p, by correlating its expression to the clinical and echocardiographic parameters of CKCSs affected by MMVD at different ACVIM stages.…”

“…In dogs affected by MMVD, upregulation of cfa-miR-130b was documented [20]. In 2022, Bagardi et al [7] measured the concentration of miR-1-3p, miR30b-5p, and miR-128-3p in 33 CKCSs of ACVIM stage B1 divided into three age-related groups, and 11 ACVIM stage A CKCSs. MiR-30b-5p was significantly higher in ACVIM B1 dogs than in ACVIM A subjects.…”

“…The identification of reliable biomarkers may enhance the robustness of clinical decision-making and may pave the way for the development of alternative/complementary diagnostic strategies [7]. In recent years, the study of microRNAs (miRNAs) increased.…”

Prospective pilot study on the predictive significance of plasma miR-30b-5p through the study of echocardiographic modifications in Cavalier King Charles Spaniels affected by different stages of myxomatous mitral valve disease: The PRIME study

“…The identification of reliable biomarkers may enhance the robustness of clinical decision-making and may pave the way for the development of alternative/complementary diagnostic strategies [ 7 ]. In recent years, the study of microRNAs (miRNAs)as promising diagnostic and prognostic biomarkers for the detection of disease increased [ 8 ].…”