12 research outputs found
Analytical Validation of a Flow Cytometric Protocol for Circulating Platelet Microparticle Quantification in Dogs
Serotonin concentrations in platelets, plasma, mitral valve leaflet, and left ventricular myocardial tissue in dogs with myxomatous mitral valve disease
HYPOTHESIS/OBJECTIVES: Altered serotonin (5âhydroxytryptamine, 5HT) signaling is postulated in development and progression of canine myxomatous mitral valve disease (MMVD). Little is known regarding platelet, plasma, valvular, or myocardial 5HT concentration ([5HT]) in affected dogs. We quantified [5HT] in plateletârich plasma (PRP), plateletâpoor plasma (PPP), mitral valve leaflets (MV), and left ventricular myocardium (LV). ANIMALS: Fortyâfive dogs comprised 4 plasma groups of Cavalier King Charles Spaniels (CKCS) or nonâCKCS, either healthy (CON) or MMVD affected: CKCS CON (n = 12); nonâCKCS CON (n = 8); CKCS MMVD (n = 14); nonâCKCS MMVD (n = 11). Twentyâfour dogs comprised 3 tissue groups: MMVD (n = 8); otherâHD (heart disease) (n = 7); nonâHD, extracardiac disease (n = 9). METHODS: Highâperformance liquid chromatography measured PRP, PPP, MV, and LV [5HT]. RESULTS: Plateletârich plasma platelet [5HT] was greater in CKCS CON (1.83 femtograms/platelet [fg/plt]; range, 0.20â4.76; P = .002), CKCS MMVD (1.58 fg/plt; range, 0.70â4.03; P = .005), and nonâCKCS MMVD (1.72 fg/plt; range, 0.85â4.44; P = .003) versus nonâCKCS CON (0.92 fg/plt; range, 0.63â1.30). There was no group difference in PPP [5HT]. MV [5HT] was significantly higher in MMVD (32.4 ng/mg; range, 8.4â106.7) versus nonâHD (3.6 ng/mg; range, 0â28.3; P = .01) and LV [5HT] was significantly higher in MMVD (11.9 ng/mg; range, 4.0â104.8) versus otherâHD (0.9 ng/mg; range, 0â10.1; P = .011) and nonâHD (2.5 ng/mg; range, 0â6.9; P = .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Platelet [5HT] was highest in healthy CKCS and both MMVD groups, but plasma [5HT] showed no group differences. Tissue [5HT] was highest in MV and LV of MMVDâaffected dogs, suggesting altered 5HT signaling as a potential feature of MMVD. Interactions of platelet, valvular, and myocardial 5HT signaling warrant further investigation
High-level serotonin binding in subpopulation of highly activated platelets in cavalier King charles spaniels with myxomatous mitral valve disease
Development of left ventricular hypertrophy in a novel porcine model of mitral regurgitation
Plasma and serum serotonin concentrations and surface-bound platelet serotonin expression in Cavalier King Charles Spaniels with myxomatous mitral valve disease
Alpha-smooth muscle actin and serotonin receptors 2A and 2B in dogs with myxomatous mitral valve disease
Plasma proANP and SDMA and microRNAs are associated with chronic mitral regurgitation in a pig model
OBJECTIVE: Non-ischemic mitral regurgitation (MR) is primarily caused by myxomatous mitral valve (MV) disease leading to adaptive remodeling, enlargement, and dysfunction of the left ventricle. The aim of this study was to examine the regulation of plasma markers and several cardiac key genes in a novel porcine model of non-ischemic MR. METHODS AND RESULTS: Twenty-eight production pigs (Sus scrofa) were randomized to experimental MR or sham surgery controls. MR was induced by external suture(s) through the posterior MV leaflet and quantified using echocardiography. The experimental group was subdivided into mild MR (mMR, MR=20â50%, n=10) and moderate/severe MR (sMR, MR >50%, n=6) and compared with controls (CON, MR â¤10%, n=12). Eight weeks postoperatively, follow-up examinations were performed followed by killing. Circulating concentrations of pro-atrial natriuretic peptide (proANP), l-arginine, asymmetric dimethylarginine, and symmetric dimethylarginine (SDMA) were measured. MV, anterior papillary muscle, and left ventricular free wall tissues were collected to quantify mRNA expression of eNOS (NOS3), iNOS (NOS2), MMP9, MMP14, ANP (NPPA), BNP (NPPB), and TGFB1, 2, and 3 and five microRNAs by quantitative real-time PCR. Pigs with sMR displayed markedly increased plasma proANP and SDMA concentrations compared with both controls and mMR (P<0.05). The expression of all genes examined differed significantly between the three localizations in the heart. miR-21 and miR-133a were differently expressed among the experimental groups (P<0.05). CONCLUSIONS: Plasma proANP and SDMA levels and tissue expression of miR-21 and miR-133a are associated with severity of chronic MR in an experimental porcine model