Is overactive bladder microvasculature disease a component of systemic atheroscleorosis?

AIMS: To evaluate the relationship between overactive bladder (OAB) and systemic atherosclerosis in a cohort of women. METHODS: In this case-control study, we assessed atherosclerosis indicators, such as Framingham risk scores and carotid and femoral artery intima-media thickness, and evaluated possible bladder wall responses to atherosclerosis using endovaginal color Doppler ultrasound and the detection of urinary cytokines in women with OAB and in controls. Quantitative assessment of blood perfusion at the bladder neck was performed using a method that allows for the dynamic monitoring of flow in a predefined region of interest at every point of the cardiac cycle. The independent samples t-test was used to evaluate the relationship between OAB and the atherosclerotic findings when parametric conditions were met, and the Mann-Whitney U test was used when parametric conditions were not met. Kendall's Tau was used to assess the correlation between OAB severity and the atherosclerotic variables. P < 0.05 was considered statistically significant. RESULTS: There were 74 OAB patients and 73 controls; in total, 147 women were evaluated. We found that all atherosclerosis indicators were significantly associated with OAB and that there was a significant relationship between OAB and decreased bladder neck perfusion. Additionally, there were correlations of OAB severity with systemic atherosclerosis and impaired vascular perfusion of the bladder. CONCLUSIONS: Decreased perfusion at the bladder neck, the Framingham scores in severe OAB, and the correlation between them suggest that OAB microvascular disease may be a component of systemic atherosclerosis rather than a separate process.

Transcriptional profiling of septal wall of the right ventricular outflow tract in patients with idiopathic ventricular arrhythmias.

BACKGROUND: Frequent, monomorphic premature ventricular contractions (PVC) and/or ventricular tachycardia (VT) in patients with structurally normal heart usually arise from the right ventricular outflow tract (RVOT). The underlying arrhythmogenic substrate for the genesis of RVOT tachycardias is largely unknown. The aim of this study was to investigate the genome-wide transcriptional profiling of the septal wall of the RVOT in patients with RVOT tachycardia and control subjects. METHODS: Transcriptional profiling with Affymetrix 3' IVT microarray analysis (Affymetrix, Santa Clara, CA, USA) was performed on the endomyocardial biopsy samples obtained from the septal wall of the RVOT from three unrelated patients with RVOT tachycardia and three control subjects. All study subjects had normal right and left ventricular size and function. Microarray results were validated by real time polymerase chain reaction (PCR). RESULTS: There were 32 statistically significant up-regulated and 60 down-regulated genes in five biological networks in patient population compared with control subjects. Among those genes, there were eight down-regulated [ATP1A2, CACNA1C, Protein Phosphatase 2, Regulatory Subunit B, Gamma Isoform[PPP2R2C], PLCD3, GNAO1, Solute Carrier Family 6 (Transporter, Norepinephrine), Member 2(SLC6A2), CAMK2B, PIK3R2] and two up-regulated (CAMKK2 and ITPR3) genes related to myocardial intracellular calcium regulation. In addition, there were five down-regulated [T-box 3(TBX3), Bone Morphogenetic Protein 2(BMP2), Bone Morphogenetic Protein Receptor, Type IB(BMPR1B), MYH6, Ankyrin Repeat Domain 23 and 39(ANKRD23-39)] and one up-regulated gene (RGS1) related to cardiovascular functions. CONCLUSION: The expression of genes responsible for the regulation of myocardial intracellular calcium and the development of RVOT are significantly down-regulated in the septal wall of the RVOT in patients with RVOT tachycardia compared with control subjects.

Increased myocardial collagen turnover in patients with progressive cardiac conduction disease.

BACKGROUND: Histopathologically, progressive cardiac conduction disease (PCCD) is characterized by progressive fibrosis and sclerodegenerative changes in the proximal and distal conduction system of the heart. Therefore, we sought to determine the serum levels of myocardial collagen turnover markers, extracellular matrix components, transforming growth factor beta(1) (TGFbeta(1)), and bone morphogenic protein-7 (BMP-7) in this population. METHODS: Study population included 20 patients (6 M/14 F, mean age 76 +/- 8 years) with acquired, permanent 2:1, or complete atrioventricular block and compared with age- and sex-matched, asymptomatic, healthy control subjects (n = 18, 6 M/12 F, mean age 75 +/- 7 years). Serum myocardial collagen turnover markers:matrix metalloproteinases (MMP-1, 2, 9), tissue inhibitor of matrix metalloproteinase (TIMP-1), amino-terminal propeptide of procollagen type I (PINP) and type III (PIIINP), carboxy-terminal telopeptide of collagen type I (CITP), and carboxy-terminal propeptide of procollagen type I (PICP), serum extracellular matrix components (laminin and fibronectin), TGFbeta(1), and BMP-7 levels were measured in both groups. RESULTS: Serum PICP (849 +/- 396 vs 631 +/- 294 ng/mL, P = 0.04), PIIINP (3.7 +/- 1.3 vs 3 +/- 1 mug/L, P = 0.03), CITP (0.68 +/- 0.35 vs 0.48 +/- 0.25 ng/mL, P = 0.037), and plasma MMP-9 (58.8 +/- 56 vs 25.9 +/- 17.3 ng/mL, P = 0.006) levels were higher in patient population compared to control subjects. Serum MMP-1 (24.1 +/- 20.5 vs 13.6 +/- 7.5 ng/mL, P = 0.045) and MMP-2 (1310 +/- 139 vs 1186 +/- 163 ng/mL, P = 0.01) levels were higher in control subjects compared to patient population. There was no difference in serum TIMP-1, PINP, laminin, fibronectin, TGFbeta(1), and BMP-7 levels between two groups. CONCLUSION: Our findings demonstrate the presence of increased myocardial collagen turnover and active fibrotic process in patients with PCCD compared to control subjects.