Background: Myxomatous mitral valve disease (MVD) is the most common acquired heart disease in dogs, and the Cavalier King Charles Spaniel (CKCS) is the most studied breed because of the high prevalence, early onset and hereditary component evidenced in the breed. MVD has different severity levels, and there are many practical limitations in identifying its asymptomatic stages. Proteomic techniques are valuable for studying the proteins and peptides involved in cardiovascular diseases, including the period prior to the clinical onset of the disease. The aim of this study was to identify the serum proteins that were differentially expressed in healthy CKCS and those affected by MVD in mild to severe stages. Proteomics analysis was performed using two-dimensional gel electrophoresis separation and a bioinformatics analysis for the detection of differentially expressed spots. In a comparative analysis, protein spots with a p<0.05 (ANOVA) were considered statistically significant and were excised from the gels for analysis by MALDI-TOF-MS for protein identification. Results: Eight proteins resulted differentially expressed among the groups and significantly related to the progression of the disease. In mild affected group versus healthy dogs complement factor H isoform 2, inhibitor of carbonic anhydrase, hemopexin, dystrobrevin beta isoform X7 and CD5 molecule-like resulted to be down-regulated, whereas fibronectin type-III domain-containing protein 3A isoform X4 was up-regulated. In severe affected dogs versus healthy group complement factor H isoform 2, calpain-3 isoform X2, dystrobrevin beta isoform X7, CD5 molecule-like and l-2-hydroxyglutarate dehydrogenase resulted to be down-regulated. Complement factor H isoform 2, calpain-3 isoform X2, dystrobrevin beta isoform X7, CD5 molecule-like and hydroxyglutarate dehydrogenase were found to be down-regulated in mild affected group versus healthy dogs. All of these proteins except complement factor H followed a decreasing trend according to the progression of the pathology. Conclusion: The differential expression of serum proteins demonstrates the possibility these might be valuable for the detection and monitoring of the disease. Further longitudinal studies are required to determine whether differential protein expression occurs sufficiently early in the progression of the disease and with sufficient predictive value to allow proteomics analysis to be used as an early detection and on-line diagnostic tool.

Serum proteomic profiles in CKCS with Mitral valve disease / C. Locatelli, C. Piras, G. Riscazzi, I. Alloggio, I. Spalla, A. Soggiu, V. Greco, L. Bonizzi, P. Roncada, P.G. Brambilla. - In: BMC VETERINARY RESEARCH. - ISSN 1746-6148. - 13:1(2017 Feb 07), p. 43.43. [10.1186/s12917-017-0951-5]

Serum proteomic profiles in CKCS with Mitral valve disease

C. Locatelli
Primo
;
C. Piras
Secondo
;
G. Riscazzi;I. Alloggio;I. Spalla;A. Soggiu;L. Bonizzi;P.G. Brambilla
2017

Abstract

Background: Myxomatous mitral valve disease (MVD) is the most common acquired heart disease in dogs, and the Cavalier King Charles Spaniel (CKCS) is the most studied breed because of the high prevalence, early onset and hereditary component evidenced in the breed. MVD has different severity levels, and there are many practical limitations in identifying its asymptomatic stages. Proteomic techniques are valuable for studying the proteins and peptides involved in cardiovascular diseases, including the period prior to the clinical onset of the disease. The aim of this study was to identify the serum proteins that were differentially expressed in healthy CKCS and those affected by MVD in mild to severe stages. Proteomics analysis was performed using two-dimensional gel electrophoresis separation and a bioinformatics analysis for the detection of differentially expressed spots. In a comparative analysis, protein spots with a p<0.05 (ANOVA) were considered statistically significant and were excised from the gels for analysis by MALDI-TOF-MS for protein identification. Results: Eight proteins resulted differentially expressed among the groups and significantly related to the progression of the disease. In mild affected group versus healthy dogs complement factor H isoform 2, inhibitor of carbonic anhydrase, hemopexin, dystrobrevin beta isoform X7 and CD5 molecule-like resulted to be down-regulated, whereas fibronectin type-III domain-containing protein 3A isoform X4 was up-regulated. In severe affected dogs versus healthy group complement factor H isoform 2, calpain-3 isoform X2, dystrobrevin beta isoform X7, CD5 molecule-like and l-2-hydroxyglutarate dehydrogenase resulted to be down-regulated. Complement factor H isoform 2, calpain-3 isoform X2, dystrobrevin beta isoform X7, CD5 molecule-like and hydroxyglutarate dehydrogenase were found to be down-regulated in mild affected group versus healthy dogs. All of these proteins except complement factor H followed a decreasing trend according to the progression of the pathology. Conclusion: The differential expression of serum proteins demonstrates the possibility these might be valuable for the detection and monitoring of the disease. Further longitudinal studies are required to determine whether differential protein expression occurs sufficiently early in the progression of the disease and with sufficient predictive value to allow proteomics analysis to be used as an early detection and on-line diagnostic tool.
Cavalier King Charles Spaniel; Dog; Mitral valve disease; Proteomic analysis; Animals; Blood Proteins; Breeding; Case-Control Studies; Dog Diseases; Dogs; Female; Heart Valve Diseases; Male; Mitral Valve; Proteomics; Proteome; Veterinary (all)
Settore VET/08 - Clinica Medica Veterinaria
Settore VET/05 - Malattie Infettive degli Animali Domestici
Settore MED/07 - Microbiologia e Microbiologia Clinica
Settore BIO/10 - Biochimica
7-feb-2017
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297119/
Article (author)
File in questo prodotto:
File Dimensione Formato  
12917_2017_Article_951.pdf

accesso aperto

Descrizione: articolo
Tipologia: Publisher's version/PDF
Dimensione 744.39 kB
Formato Adobe PDF
744.39 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/479282
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 12
social impact