Platelet proteome changes in dogs with congestive heart failure

Abstract

Background Platelets play a central role in the development of cardiovascular diseases and changes in their proteins are involved in the pathophysiology of heart diseases in humans. There is lack of knowledge about the possible role of platelets in congestive heart failure (CHF) in dogs. Thus, this study aimed to investigate the changes in global platelet proteomes in dogs with CHF, to clarify the possible role of platelets in the physiopathology of this disease. Healthy-dogs (n = 10) and dogs with acute CHF due to myxomatous mitral valve disease (MMVD, n = 10) were used. Acute CHF was defined based on the clinical (increased respiratory rate or difficulty breathing) and radiographic findings of pulmonary edema. Dogs Blood samples were collected into tubes with acid-citrate-dextrose, and platelet-pellets were obtained by centrifuge and washing steps. Platelet-proteomes were identified using LC-MS based label-free differential proteome expression analysis method and matched according to protein database for Canis lupus familiaris. Results Totally 104 different proteins were identified in the platelets of the dogs being 4 out of them were significantly up-regulated and 6 down-regulated in acute CHF dogs. Guanine-nucleotide-binding protein, apolipoproteins (A-II and C-III) and clusterin levels increased, but CXC-motif-chemokine-10, cytochrome-C-oxidase-subunit-2, cathepsin-D, serine/threonine-protein-phosphatase-PP1-gamma-catalytic-subunit, creatine-kinase-B-type and myotrophin levels decreased in acute CHF dogs. These proteins are associated with several molecular functions, biological processes, signaling systems and immune-inflammatory responses. Conclusion This study describes by first time the changes in the protein composition in platelets of dogs with acute CHF due to MMVD. Our findings provide a resource for increase the knowledge about the proteome of canine platelets and their roles in CHF caused by MMVD and could be a tool for further investigations about the prevention and treatment of this disease.

Serum Proteomic Changes in Dogs with Different Stages of Chronic Heart Failure

“…For the assessment of cardiac geometry and function, a transthoracic echocardiographic examination was performed as previously suggested [ 12 , 13 , 16 ]. Cardiac measurements were performed using conventional modalities (2-D, M-mode, and color Doppler) and imaging techniques (right parasternal short and long axis, left apical 4–5 chamber and subcostal views) with phased-array cardiac transducers (2.5–5, 5–7.5 or 7.5–10 MHz) selected according to body weight and the size of the dogs (Caris Plus Esaote, Genoa, Italy).…”

“…Two weeks after the initiation of the medical therapy, all dogs were re-examined, but only data collected from dogs in stage C were used, to evaluate changes in the proteins after treatment. Stage D dogs were not preferred for this comparison, because the drugs used to relieve the clinical signs of CHF before being enrolled into the study could affect the protein composition in such dogs, as reported in our previous study [ 16 ].…”

“…In a previous study [ 11 ], we saw that there are changes in serum components in dogs at different stages of CHF due to MMVD, and that it would be of interest to evaluate whether there are more proteins that can change. Proteomics studies serve these purposes by identifying thousands of low-molecular-weight proteins in biological samples such as serum [ 12 , 13 ], myocardial tissue [ 14 , 15 ] and platelets [ 16 ], and determining protein–protein interactions [ 12 , 13 , 16 ].…”

“…Previous research using proteomic analysis of myocardial tissue has identified new pathophysiological mechanisms contributing to cardiovascular diseases such as ischemic cardiomyopathy [ 15 ], dilated cardiomyopathy (DCM) [ 14 ], diabetic cardiomyopathy [ 17 , 18 ], and atherosclerosis [ 19 ]. Recently, we showed changes in platelet proteins, such as clusterin, CXC-motif-chemokine, cathepsin, creatine-kinase-B and myotrophin, to be associated with cellular, biologic, metabolic, immune, and coagulation system processes involved in the development of CHF caused by MMVD in dogs [ 16 ]. Although there are limited studies on serum proteomics in dogs with MMVD [ 13 ], idiopathic DCM [ 20 , 21 ] and CHF [ 12 ], there are no data about possible changes in proteins depending on the severity of CHF associated with MMVD and the evolution of these proteins after standard treatment.…”

Urinary Proteomic Signature in Acute Decompensated Heart Failure: Advances into Molecular Pathophysiology

“…Differential proteome signatures between normal and disease states can be determined by using targeted and untargeted mass spectrometry (MS)-based proteomic approaches [9,10]. MS analysis has emerged as a powerful tool in proteomics to identify and characterize proteins and protein complexes in biological samples including blood, urine, tissues, and cells.…”