Coronary computed tomography angiography investigation of the association between left main coronary artery bifurcation angle and risk factors of coronary artery disease

To explore the association between the left main coronary artery bifurcation angle and common atherosclerotic risk factors with regard to the development of coronary artery disease (CAD) using coronary computed tomography angiography (CCTA). A retrospective review of 196 CCTA cases (129 males, 67 females, mean age 58 ± 10.5 years) was conducted. The bifurcation angle between the left anterior descending (LAD) and left circumflex (LCx) was measured on two-dimensional (2D) and three-dimensional (3D) reconstructed images and the type of plaque and degree of lumen stenosis was assessed to determine the disease severity. An association between bifurcation angle and patient risk factors [gender, body mass index (BMI), hypertension, cholesterol, diabetes, smoking and family history] of CAD was also assessed to demonstrate the relationship between these variables. The mean bifurcation angle between the LAD and LCx was 79.40° ± 22.97°, ranging from 35.5° to 178°. Gender and BMI were found to have significant associations with bifurcation angle. Males were at 2.07-fold greater risk of having a >80° bifurcation angle and developing CAD than females (P = 0.003), and patients with high BMI (>25 kg/m2) were 2.54-fold more likely to have a >80° bifurcation angle than patients with a normal BMI (P = 0.001) and thus were at greater risk of developing CAD. There is a direct relationship between the left main coronary artery bifurcation angle and patient gender and BMI. Measurement of the bifurcation angle should be incorporated into clinical practice to identify patients at high risk of developing CAD

Importance of Non-Selective Cation Channel TRPV4 Interaction with Cytoskeleton and Their Reciprocal Regulations in Cultured Cells

BACKGROUND: TRPV4 and the cellular cytoskeleton have each been reported to influence cellular mechanosensitive processes as well as the development of mechanical hyperalgesia. If and how TRPV4 interacts with the microtubule and actin cytoskeleton at a molecular and functional level is not known. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated the interaction of TRPV4 with cytoskeletal components biochemically, cell biologically by observing morphological changes of DRG-neurons and DRG-neuron-derived F-11 cells, as well as functionally with calcium imaging. We find that TRPV4 physically interacts with tubulin, actin and neurofilament proteins as well as the nociceptive molecules PKCepsilon and CamKII. The C-terminus of TRPV4 is sufficient for the direct interaction with tubulin and actin, both with their soluble and their polymeric forms. Actin and tubulin compete for binding. The interaction with TRPV4 stabilizes microtubules even under depolymerizing conditions in vitro. Accordingly, in cellular systems TRPV4 colocalizes with actin and microtubules enriched structures at submembranous regions. Both expression and activation of TRPV4 induces striking morphological changes affecting lamellipodial, filopodial, growth cone, and neurite structures in non-neuronal cells, in DRG-neuron derived F11 cells, and also in IB4-positive DRG neurons. The functional interaction of TRPV4 and the cytoskeleton is mutual as Taxol, a microtubule stabilizer, reduces the Ca2+-influx via TRPV4. CONCLUSIONS AND SIGNIFICANCE: TRPV4 acts as a regulator for both, the microtubule and the actin. In turn, we describe that microtubule dynamics are an important regulator of TRPV4 activity. TRPV4 forms a supra-molecular complex containing cytoskeletal proteins and regulatory kinases. Thereby it can integrate signaling of various intracellular second messengers and signaling cascades, as well as cytoskeletal dynamics. This study points out the existence of cross-talks between non-selective cation channels and cytoskeleton at multiple levels. These cross talks may help us to understand the molecular basis of the Taxol-induced neuropathic pain development commonly observed in cancer patients