Putative Circulating MicroRNAs Are Able to Identify Patients with Mitral Valve Prolapse and Severe Regurgitation.

Mitral valve prolapse (MVP) associated with severe mitral regurgitation is a debilitating disease with no pharmacological therapies available. MicroRNAs (miRNA) represent an emerging class of circulating biomarkers that have never been evaluated in MVP human plasma. Our aim was to identify a possible miRNA signature that is able to discriminate MVP patients from healthy subjects (CTRL) and to shed light on the putative altered molecular pathways in MVP. We evaluated a plasma miRNA profile using Human MicroRNA Card A followed by real-time PCR validations. In addition, to assess the discriminative power of selected miRNAs, we implemented a machine learning analysis. MiRNA profiling and validations revealed that miR-140-3p, 150-5p, 210-3p, 451a, and 487a-3p were significantly upregulated in MVP, while miR-223-3p, 323a-3p, 340-5p, and 361-5p were significantly downregulated in MVP compared to CTRL (p ≤ 0.01). Functional analysis identified several biological processes possible linked to MVP. In addition, machine learning analysis correctly classified MVP patients from CTRL with high accuracy (0.93) and an area under the receiving operator characteristic curve (AUC) of 0.97. To the best of our knowledge, this is the first study performed on human plasma, showing a strong association between miRNAs and MVP. Thus, a circulating molecular signature could be used as a first-line, fast, and cheap screening tool for MVP identification.

The chromogranin A-derived peptides catestatin and vasostatin in dogs with myxomatous mitral valve disease.

BACKGROUND: The protein chromogranin A (CgA) is stored and co-released with catecholamines from the stimulated adrenal glands. Increased plasma concentrations of CgA have been shown in people with heart disease. The aim of the study was to investigate whether plasma concentrations of the CgA-derived biologically active peptides catestatin and vasostatin were associated with the severity of myxomatous mitral valve disease (MMVD) in dogs and to assess potential associations between these blood variables and dog characteristics, echocardiographic variables, heart rate (HR), blood pressure (BP) and plasma N-terminal-proBNP (NT-proBNP) concentration. Sixty-seven privately owned dogs with or without MMVD were included. The dogs underwent physical examination, blood pressure measurement, blood sample collection, and echocardiographic examination. Plasma concentrations of catestatin and vasostatin were analyzed using radioimmunoassay. RESULTS: Catestatin concentration decreased with increasing left atrial and ventricular size (R2 ≤ 0.09, P ≤ 0.019), and increased with increasing systolic and diastolic blood pressures (R2 ≤ 0.08, P ≤ 0.038). Regression analyses showed no significant associations for vasostatin. No differences in plasma concentrations of catestatin or vasostatin were found between the disease severity groups used in the study. CONCLUSIONS: In the present dog population, the catestatin concentration showed weak negative associations with left atrial and ventricular sizes, both of which are known to increase with increasing severity of MMVD. Furthermore, the catestatin concentration showed weak positive associations with blood pressure.

Monocyte to high-density lipoprotein ratio: a prognostic factor for mitral valve prolapse?

BACKGROUND: Mitral valve prolapse (MVP) is a common disorder, afflicting 2 % to 3 % of the general population. Despite the general belief of a benign disorder, there is an increasing awareness of an association between mitral valve prolapse and sudden cardiac death from arrhythmia and also atherosclerosis. Monocyte to high density lipoprotein ratio (MHR) is a new tool for predicting inflammation, which plays a major role in atherosclerosis. OBJECTIVE:   To evaluate the relationship between MHR and the presence of MVP. METHODS: The study population consisted of 82 patients with MVP and the control group of 78 normal individuals. Transthoracic echocardiograpy was performed for all of the study population and peripheral venous blood samples were drawn for measuring MHR and other haemotological parameters. RESULTS: The patients with MVP were more likely to have higher MHR values (15.82±6.01 in MVP patients and 13.30 ± 6.43 in controls; p=0.011). Monocyte counts and MHR of the MVP group were significantly higher than the control group and MHR values were directly proportional with the regurgitation area. CONCLUSION: The MHR is strongly associated with MVP and regurgitation area and might be a prognostic factor for patients with MVP (Tab. 3, Fig. 1, Ref. 15).

Comprehensive microRNA profiling reveals potential augmentation of the IL1 pathway in rheumatic heart valve disease.

BACKGROUND: Valvular heart disease is a leading cause of cardiovascular mortality, especially in China. More than a half of valvular heart diseases are caused by acute rheumatic fever. microRNA is involved in many physiological and pathological processes. However, the miRNA profile of the rheumatic valvular heart disease is unknown. This research is to discuss microRNAs and their target gene pathways involved in rheumatic heart valve disease. METHODS: Serum miRNA from one healthy individual and four rheumatic heart disease patients were sequenced. Specific differentially expressed miRNAs were quantified by Q-PCR in 40 patients, with 20 low-to-moderate rheumatic mitral valve stenosis patients and 20 severe mitral valve stenosis patients. The target relationship between certain miRNA and predicted target genes were analysis by Luciferase reporter assay. The IL-1ß and IL1R1 expression levels were analyzed by immunohistochemistry and western blot in the mitral valve from surgery of mitral valve replacement. RESULTS: The results showed that 13 and 91 miRNAs were commonly upregulated or downregulated in all four patients. Nine miRNAs, 1 upregulated and 8 downregulated, that had a similar fold change in all 4 patients were selected for quantitative PCR verification. The results showed similar results from miRNA sequencing. Within these 9 tested miRNAs, hsa-miR-205-3p and hsa-miR-3909 showed a low degree of dispersion between the members of each group. Hsa miR-205-3p and hsa-miR-3909 were predicted to target the 3'UTR of IL-1ß and IL1R1 respectively. This was verified by luciferase reporter assays. Immunohistochemistry and Western blot results showed that the mitral valve from rheumatic valve heart disease showed higher levels of IL- 1ß and IL1R1 expression compared with congenital heart valve disease. This suggested a difference between rheumatic heart valve disease and other types of heart valve diseases, with more inflammatory responses in the former. CONCLUSION: In the present study, by next generation sequencing of miRNAs, it was revealed that interleukin 1ß and interleukin 1 receptor 1 was involved in rheumatic heart diseases. And this is useful for diagnosis and understanding of mechanism of rheumatic heart disease.

Identification of Patients Affected by Mitral Valve Prolapse with Severe Regurgitation: A Multivariable Regression Model.

Background. Mitral valve prolapse (MVP) is the most common cause of severe mitral regurgitation. Besides echocardiography, up to now there are no reliable biomarkers available for the identification of this pathology. We aim to generate a predictive model, based on circulating biomarkers, able to identify MVP patients with the highest accuracy. Methods. We analysed 43 patients who underwent mitral valve repair due to MVP and compared to 29 matched controls. We assessed the oxidative stress status measuring the oxidized and the reduced form of glutathione by liquid chromatography-tandem mass spectrometry method. Osteoprotegerin (OPG) plasma levels were measured by an enzyme-linked immunosorbent assay. The combination of these biochemical variables was used to implement several logistic regression models. Results. Oxidative stress levels and OPG concentrations were significantly higher in patients compared to control subjects (0.116 ± 0.007 versus 0.053 ± 0.013 and 1748 ± 100.2 versus 1109 ± 45.3 pg/mL, respectively; p < 0.0001). The best regression model was able to correctly classify 62 samples out of 72 with accuracy in terms of area under the curve of 0.92. Conclusions. To the best of our knowledge, this is the first study to show a strong association between OPG and oxidative stress status in patients affected by MVP with severe regurgitation.

Serum Concentrations of Leptin and Adiponectin in Dogs with Myxomatous Mitral Valve Disease.

BACKGROUND: The concentrations of circulating adipokines in dogs with myxomatous mitral valve disease (MMVD) have not been investigated in detail. OBJECTIVES: To determine whether serum concentrations of adipokines differ between healthy dogs and dogs with MMVD and whether circulating concentrations depend on the severity of heart failure resulting from MMVD. ANIMALS: In the preliminary study, 30 healthy dogs and 17 client-owned dogs with MMVD, and in the subsequent study, 30 healthy dogs and 46 client-owned dogs with MMVD. METHODS: Prospective case-controlled observational study. In the preliminary study, serum concentrations of leptin, adiponectin, resistin, visfatin, interleukin (IL)-1ß, IL-6, IL-10, IL-18, and tumor necrosis factor-α were measured. In the subsequent study, MMVD dogs were divided into three groups according to the International Small Animal Cardiac Health Council (ISACHC) classification, and serum concentrations of leptin and adiponectin were measured. RESULTS: In the preliminary study, serum leptin and adiponectin concentrations differed significantly between dogs with MMVD and healthy dogs. Serum leptin (P = .0013) concentrations were significantly higher in dogs with MMVD than in healthy dogs, whereas adiponectin (P = .0009) concentrations were significantly lower in dogs with MMVD. However, we observed no significant differences in the other variables. In the subsequent study, dogs classified as ISACHC class 3 had higher serum concentrations of leptin (P = .0022) than healthy dogs but ISACHC class 1 or 2 dogs did not. Serum adiponectin concentrations were significantly lower in ISACHC class 1 (P < .0001) dogs than in healthy dogs, whereas adiponectin concentrations in ISACHC class 3 dogs were significantly higher than in ISACHC class 1 dogs (P = .0081). CONCLUSIONS AND CLINICAL IMPORTANCE: Circulating concentrations of leptin and adiponectin might be altered in dogs with MMVD.

Rheumatic Disease Autoantibodies in Autoimmune Liver Diseases.

BACKGROUND: Autoimmune liver diseases (ALDs) are known to be associated with systemic autoimmune rheumatic diseases (SARDs) and their autoantibodies. We aimed to study the prevalence of SARDs and related autoantibodies, as well as their prognostic implications in a group of patients with ALDs. METHODS: This was a cross-sectional study. Sixty patients with ALDs (38.3% with autoimmune hepatitis; 11.7% with primary biliary cirrhosis; 25% with primary sclerosing cholangitis and 25% with overlap syndrome) were studied for the presence of SARDs and their autoantibodies. RESULTS: There was autoimmune rheumatic disease in 20% of the studied sample. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were the commonest (11.6% and 5%, respectively). Antinuclear antibodies (ANAs) were present in 35% of the patients, followed by anti-Ro (20.0%); anti-nucleosome (18.3%); rheumatoid factor (10%) anti-CCP (8.3%); anti-RNP (8.3%); anti-ds-DNA (6.6%); anti-La (3.3%); anti-Sm (3.3%), anti-ribosomal P (3.3%). Anti-Ro (p = 0.0004), anti-La (p = 0.03), anti-RNP (p = 0.04) and anti-Sm (p = 0.03) were commonly found in patients with SARD, but not anti-DNA, anti-nucleosome and anti-ribosomal P. No differences were found in liver function tests regarding to the presence of autoantibodies. CONCLUSIONS: There was a high prevalence of SARD and their autoantibodies in ALD patients. Anti-Ro, anti-La, anti-RNP and anti-Sm positivity points to an association with systemic autoimmune rheumatic diseases. The presence of autoantibodies was not related to liver function tests.

Functional state of sportsmen with mitral valve prolapse.

The study covered functional peculiarities in 541 professional sportsmen. Mitral valve prolapse (in 132 examinees) appeared to be associated with reliably lower levels of reticulocytes, leucocytes, lymphocytes CD4+, immunoglobulines G, magnesium, and higher cortisol level, in comparison with the sportsmen having no mitral valve prolapse. The athletes with mitral valve prolapse demonstrated more frequent changes in ECG, reliably lower performance in treadmill test, slower recovery of heart rate after exertion is over.

Expression Profiling of Circulating MicroRNAs in Canine Myxomatous Mitral Valve Disease.

MicroRNAs (miRNAs) are small non-coding RNAs that have shown promise as noninvasive biomarkers in cardiac disease. This study was undertaken to investigate the miRNA expression profile in dogs with myxomatous mitral valve disease (MMVD). 277 miRNAs were quantified using RT-qPCR from six normal dogs (American College of Veterinary Internal Medicine Stage A), six dogs with MMVD mild to moderate cardiac enlargement (ACVIM Stage B1/B2) and six dogs with MMVD and congestive heart failure (ACVIM Stage C/D). Eleven miRNAs were differentially expressed (False Discovery Rate < 0.05). Dogs in Stage B1/B2 or C/D had four upregulated miRNAs, including three cfa-let-7/cfa-miR-98 family members, while seven others were downregulated, compared to Stage A. Expression of six of the 11 miRNAs also were significantly different between dogs in Stage C/D and those in Stage B1/B2. The expression changes were greater as disease severity increased. These miRNAs may be candidates for novel biomarkers and may provide insights into genetic regulatory pathways in canine MMVD.

Effect of physiological determinants and cardiac disease on plasma adiponectin concentrations in dogs.

BACKGROUND: In humans, a high concentration of adiponectin is associated with a favorable cardiovascular risk profile whereas, in patients with heart failure (HF), a high concentration of adiponectin is associated with a less favorable prognosis. HYPOTHESIS/OBJECTIVES: To evaluate the physiological determinants of plasma adiponectin concentration in dogs and the influence of heart disease, myxomatous mitral valve disease (MMVD), and dilated cardiomyopathy (DCM). ANIMALS: One hundred and fourteen client-owned dogs and 9 Beagles from the research colony of the Clinical Veterinary Unit of the University of Liège. METHODS: We prospectively measured circulating adiponectin concentration in healthy control dogs (n = 77), dogs with MMVD (n = 22) and dogs with DCM (n = 15) of various degrees of severity. Diagnosis was confirmed by Doppler echocardiography. Plasma adiponectin concentration was measured by a canine-specific sandwich ELISA kit. RESULTS: An analysis of covariance showed an association between adiponectin concentration and age, neuter status, and heart disease. No association between adiponectin concentration and class of HF, sex, body condition score, body weight, circadian rhythm, or feeding was found. Plasma adiponectin concentration was negatively correlated with age (P = .001). Adiponectin was lower in neutered (P = .008) compared to intact dogs. Circulating adiponectin concentration was increased in dogs with DCM compared to healthy dogs (P = .018) and to dogs with MMVD (P = .014). CONCLUSIONS AND CLINICAL IMPORTANCE: Age and neutering negatively influence circulating adiponectin concentration. Plasma adiponectin concentration increased in dogs with DCM. Additional research is required to investigate if this hormone is implicated in the pathophysiology of DCM and associated with clinical outcome.

Short-term effect of granulocyte colony-stimulating factor in dogs with severe myxomatous mitral valve disease.

BACKGROUND: Use of granulocyte colony-stimulating factor (G-CSF) to treat damaged myocardium is a relatively new concept. Clinical beneficial and safety outcomes are still controversial. OBJECTIVE: The aim of this study was to evaluate recruitment of hematopoietic stem cells and therapeutic efficacy of G-CSF in the treatment of myxomatous mitral valve disease (MMVD) of dogs. ANIMALS AND METHODS: Thirty client-owned MMVD dogs with clinical signs of heart failure were enrolled in a prospective double-blind, randomized, placebo-controlled study to compare the short-term effect of G-CSF (n = 17) with control group (n = 13) for identical periods. Clinical, hematological, and cardiovascular assessments were performed on days 0, 1, 3, and 7. Follow-up examination was conducted four weeks after the study. RESULTS: Dogs treated with G-CSF had a significantly elevated white blood cell (WBC) (×10(3)/µL) count at day 3 compared with baseline (from 10.23 ± 4.42 to 42.84 ± 11.84; P = .000). The WBC population was also changed (elevated neutrophils and decreased lymphocytes) and the numbers of CD34+ cells in the peripheral blood were also increased at day 3. However, the results of clinical, laboratory, and echocardiographic assessments did not differ significantly between the G-CSF treatment and control groups after four weeks. CONCLUSIONS: G-CSF administration elevated the peripheral WBC count, especially neutrophils, and recruited hematopoietic stem cells. However, positive effects of G-CSF on cardiac function were not detected during short-term monitoring.

Plasma and platelet serotonin concentrations in healthy dogs and dogs with myxomatous mitral valve disease.

OBJECTIVES: Serotonin has been implicated in canine myxomatous mitral valve disease (MMVD); however, the sources of serotonin have not been fully elucidated. This study compared the concentration of serotonin in plasma and platelets of normal healthy small breed dogs with predisposition to MMVD and dogs with naturally occurring MMVD. ANIMALS: 43 small-breed client-owned dogs with an approximate weight of <10 kg and age of 6 years or above were divided into 2 groups: a healthy control group (n = 20) and a group with echocardiographic evidence of MMVD (n = 23). METHODS: 5 ml samples of blood were collected. Plasma and platelets were separated by centrifugation and assayed for serotonin measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Median plasma serotonin concentration was not significantly different (p = 0.3630) between normal healthy dogs (3.7 ng/ml) and dogs with MMVD (4.3 ng/ml). Males had higher plasma serotonin concentration than females (4.7 and 2.9 ng/ml respectively, p = 0.0043). Platelet serotonin concentration was not different between healthy dogs and dogs with MMVD (128.6 ng/109 platelets and 176.6 ng/109 platelets respectively, p = 0.4575). Age, echocardiographic indices and platelet count showed no correlation with plasma or platelet serotonin concentration. CONCLUSIONS: Circulating plasma serotonin is unlikely a major source of serotonin signaling in canine MMVD. Platelets could be a source of serotonin in canine MMVD through platelet adhesion to the mitral valve; however, the amount of serotonin stored in platelets of healthy dogs and dogs with MMVD is not different.

Increased NT-proANP predicts risk of congestive heart failure in Cavalier King Charles spaniels with mitral regurgitation caused by myxomatous valve disease.

OBJECTIVES: To evaluate the predictive value of plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and nitric oxide end-products (NOx) as markers for progression of mitral regurgitation caused by myxomatous mitral valve disease. ANIMALS: Seventy-eight privately owned Cavalier King Charles spaniels with naturally occurring myxomatous mitral valve disease. METHODS: Prospective longitudinal study comprising 312 measurements over a 4.5 year period. Clinical values were recorded, NT-proANP concentrations were measured by radioimmunoassay, and NOx were analyzed colorimetrically. To predict congestive heart failure (CHF), Cox proportional hazards models with time-varying covariates were constructed. RESULTS: The hazard ratio for NT-proANP (per 1000 pmol/l increase) to predict future CHF was 6.7 (95% confidence interval, 3.6-12.5; p < 0.001). The median time to CHF for dogs with NT-proANP levels >1000 pmol/l was 11 months (95% confidence interval, 5.6-12.6 months), compared to 54 months (46 - infinity) for dogs with concentrations ≤ 1000 pmol/l (p < 0.001). Due to intra- and inter-individual variability, most corresponding analyses for NOx were insignificant but dogs reaching CHF had a lower mean NOx concentration than dogs not reaching CHF (23 vs. 28 µmol/l, p = 0.016). Risk of CHF increased with increase in heart rate (>130 beats per minute) and grade of murmur (≥ 3/6). CONCLUSIONS: The risk of CHF due to mitral regurgitation is increased in dogs with blood NT-proANP concentrations above 1000 pmol/l. Measurement of NT-proANP can be a valuable tool to identify dogs that may develop CHF within months.

Cardiomyopathy in young adults with classic mitral valve prolapse.

BACKGROUND: In some inherited connective tissue diseases with involvement of the cardiovascular system, for example, Marfan syndrome, early impairment of left ventricular function, which have been described as Marfan-related cardiomyopathy has been reported. Our aim was to evaluate the left ventricular function in young adults with mitral valve prolapse without significant mitral regurgitation using two-dimensional strain imaging and to determine the possible role of the transforming growth factor-ß pathway in its deterioration. METHODS: We studied 78 young adults with mitral valve prolapse without mitral regurgitation in comparison with 80 sex-matched and age-matched healthy individuals. Longitudinal strain and strain rates were defined using spackle tracking. Concentrations of transforming growth factor-ß1 and ß2 in serum were determined by enzyme-linked immunosorbent assays. RESULTS: In 29 patients, classic relapse was identified with a leaflet thickness of ≥ 5 mm; 49 patients had a non-classic mitral valve prolapse. Despite the similar global systolic function, a significant reduction in global strain was found in the classic group (-15.5 ± 2.9%) compared with the non-classic group (-18.7 ± 3.8; p = 0.0002) and the control group (-19.6 ± 3.4%; p < 0.0001). In young adults with non-classic prolapse, a reduction in longitudinal deformation was detected only in septal segments. Transforming growth factor-ß1 and ß2 serum levels were elevated in patients with classic prolapse as compared with the control group and the non-classic mitral valve prolapse group. CONCLUSIONS: These changes in the deformations may be the first signs of deterioration of the left ventricular function and the existence of primary cardiomyopathy in young adults with mitral valve prolapse, which may be caused by increased transforming growth factor-ß signalling.

Proteomics discovery of biomarkers for mitral regurgitation caused by mitral valve prolapse.

Mitral regurgitation (MR) is a common valvular lesion frequently caused by mitral valve prolapse (MVP). Surgical intervention in MVP patients with significant MR is predicated on symptoms and measures of left ventricular dysfunction. Because these indicators may be subjective or imprecise, serological biomarkers of disease could be a valuable adjunct to standard evaluation. This study aimed to identify such biomarkers by a proteomics approach. Two pooled plasma samples from 24 MVP subjects with MR (MVP/MR) and 24 non-MVP individuals were treated with the combinatorial peptide ligand library (CPLL) beads prior to iTRAQ labeling and ESI-MS/MS. Lower levels of haptoglobin, platelet basic protein (PBP), and complement component C4b were observed in the MVP/MR as compared to the control sample. These findings were verified by ELISA testing of each of the 24 paired samples, and another 42 matched cases and controls. The AUC values, sensitivities and specificities for (i) haptoglobin, (ii) PBP, (iii) C4b, and (iv) all 3 proteins in combination were (i) 0.813, 76%, 74%; (ii) 0.721, 56%, 77%; (iii) 0.689, 83%, 49%; and (iv) 0.840, 89%, 67%, respectively. In conclusion, haptoglobin, PBP, and C4b are down-regulated in MVP/MR. Their value as serological biomarkers of valvular pathology should be further explored. BIOLOGICAL SIGNIFICANCE: We report the first study that performed comparative proteomics of clinical human plasma samples to identify novel diagnostic biomarkers for mitral valve prolapse (MVP) patients with moderate to severe mitral regurgitation (MR). MR is a common valvular lesion that can be complicated by heart failure, sudden death and atrial fibrillation, yet many patients with severe MR are asymptomatic. Our results revealed reduced levels of haptoglobin, platelet basic protein (PBP), and complement component C4b in the MVP/MR patients as compared to the matched control cases. The plasma proteomics findings were subsequently confirmed by ELISA. Each of these candidate biomarkers has a putative role in the pathophysiology of MVP/MR, further supporting their roles in detection and possibly surveillance and prognostication of this disease.

Serum serotonin concentration is associated with severity of myxomatous mitral valve disease in dogs.

BACKGROUND: The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has recently been suggested to play a role in the development of naturally acquired myxomatous mitral valve disease (MMVD) in dogs. AIM: To investigate the association between serum 5-HT concentration and MMVD severity in dogs, and to assess potential associations between serum 5-HT concentrations and dog characteristics, echocardiographic variables, heart rate, systolic blood pressure, presence of macrothrombocytosis, and plateletcrit. ANIMALS: A total of 120 client-owned dogs. MATERIAL AND METHODS: Dogs were prospectively recruited and were classified by standard echocardiography into healthy (dogs of breeds predisposed to MMVD, but without echocardiographic evidence of the disease), mild, moderate, or severe MMVD groups. Serum 5-HT concentrations were analyzed using an ELISA. RESULTS: Dogs with severe MMVD had lower serum 5-HT concentrations than healthy dogs (P = .0025) and dogs with mild MMVD (P = .0011). Unilinear and multiple regression analyses showed that serum 5-HT concentrations decreased with increasing left atrial to aortic root ratio (LA/Ao), were higher in Cavalier King Charles Spaniel (CKCS) dogs compared to dogs of other breeds, and were higher in female dogs than in male dogs. The LA/Ao was the variable most strongly associated with serum 5-HT concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: The finding of higher serum 5-HT concentrations in dogs of breeds predisposed to the early onset of MMVD (CKCS) and dogs with mild MMVD suggests that alterations in 5-HT signaling might play a role in progression of early stages of MMVD.

Mean platelet volume may be elevated in mitral valve prolapse and associated with the severity of prolapse.

Thromboembolic events can be seen in patients with mitral valve prolapse (MVP). It is unclear whether platelet activation may contribute to these events in patients with MVP. Thus, we aimed to evaluate mean platelet volume (MPV) in patients with MVP and its association with the severity of MVP. This study included 312 patients with MVP and 240 control participants. Mean platelet volume was significantly higher in patients with MVP than in controls (8.9 ± 0.7 vs 7.9 ± 0.6 fL, P = .001). In linear regression analysis, MPV was independently associated with the degree of mitral regurgitation (ß = .23, 95% confidence interval (CI): 0.14-0.32, P = .001), maximal leaflet displacement (ß = .24, 95%CI: 0.17-0.31, P = .001), and mean thickness of the anterior (ß = .47, 95%CI: 0.27-0.61, P = .001) and posterior leaflets (ß = .22, 95%CI: 0.03-0.41, P = .02). Our findings show that MPV can be elevated in patients with MVP and may be independently associated with severity of mitral regurgitation, leaflet displacement, and thickness of the leaflets.

[The oxidative modifications of lipoproteins in male youths with primary mitral valve prolapse].

The sampling of 137 male youths with primary mitral valve prolapse underwent the analysis of content of lipoproteins, malonic dialdehyde and modified lipoproteins depending on conditions of adaptive reserves of organism. The decrease of adaptive reserves of organism documented by higher content of oxidized lipoproteins up to 2.84 times (p < 0.05) and malonic dialdehyde up to 1.85 times as compared with control group (p < 0.05). The reliable difference between lipidogram data in patients with high and lower adaptive reserves was not established.

[The role of transforming growth factor-ß in the pathogenesis of mitral valve prolapse].

Changes in activity of the components of TGF-ß signaling pathway is associated with inherited disorders of connective tissue such as Marfan syndrome, Loeys-Dietz syndrome, etc. However, its impact on mitral valve prolapse (MVP) has not been completely studied. We examined 35 patients undergoing reconstructive surgery due MVP complicated by severe mitral insufficiency (mean age 62.5+/-7.9 years, 46% - men). High level of TGF-ßl/2 was detected in majority (65%) of cases and correlated with the thickness of posterior leaflet (r=0.67; p=0.016), residual valve prolapse (r=0.68; p=0.007) and residual mitral regurgitation (MR) (r=0.56; p=0.01). In patients with high TGF-ßl/2 level we detected a significant decrease in left ventricular longitudinal systolic (-13.5+/-2.2% vs. -16.6+/-2.3%, p=0.008) and diastolic (1.14+/-0.20 s-1 vs. 1.34+/-0.18 s-1, p=0.04) strain and SR (-0.89+/-0.15 s-1 vs. -1.14+/-0.15 s-1, p=0.002). Thus, TGF-ß has a significant impact on the progression of valve myxomatous degeneration. The high activity of TGF-ß signaling pathway results also in reduction in LV function, probably due to the profibrotic activity.

Associations among serum N-terminal procollagen type III concentration, urinary aldosterone-to-creatinine ratio, and ventricular remodeling in dogs with myxomatous mitral valve disease.

OBJECTIVE: To assess relationships among serum N-terminal procollagen type III concentration, urinary aldosterone-to-creatinine concentration ratio (UAC), and clinical variables in dogs with myxomatous mitral valve disease (MMVD) and healthy dogs. ANIMALS: 162 dogs with MMVD and 24 healthy control dogs of comparable age and body weight. PROCEDURES: Blood and urine samples were collected from each dog. Dogs with MMVD underwent echocardiography and ECG. Ventricular diameter measurements were normalized for body weight. Serum N-terminal procollagen type III and urinary aldosterone concentrations were measured via radioimmunoassay. Each dog was examined on 1 to 3 occasions. Examinations were repeated at approximately 6-month intervals. RESULTS: Serum N-terminal procollagen type III concentration decreased with increasing severity of MMVD and was negatively associated with age and left ventricular end-diastolic and end-systolic diameters. The UAC increased with prior percentage change in left ventricular end-diastolic diameter per month, subsequent percentage change in left ventricular end-systolic diameter per month, and treatment with diuretics and was negatively associated with age. Both UAC and serum N-terminal procollagen type III concentration were higher in Cavalier King Charles Spaniels than in other breeds when other measured variables were controlled for. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with MMVD, echocardiographic indicators of left ventricular remodeling appeared to be associated with a decrease in serum concentration of a marker of collagen type III turnover and an increase in urinary aldosterone concentration.