Background Arterial stiffness and wall shear stress are powerful determinants of cardiovascular health, and arterial stiffness is associated with increased cardiovascular mortality. Low and oscillatory wall shear stress, termed disturbed flow (d-flow), promotes atherosclerotic arterial remodeling, but the relationship between d-flow and arterial stiffness is not well understood. The objective of this study was to define the role of d-flow on arterial stiffening and discover the relevant signaling pathways by which d-flow stiffens arteries. Methods D-flow was induced in the carotid arteries of young and old mice of both sexes. Arterial stiffness was quantified ex vivo with cylindrical biaxial mechanical testing and in vivo from duplex ultrasound and compared to unmanipulated carotid arteries from 80-week-old mice. Gene expression and pathway analysis was performed on endothelial cell-enriched RNA and validated by immunohistochemistry. In vitro testing of signaling pathways was performed under oscillatory and laminar wall shear stress conditions. Human arteries from regions of d-flow and stable flow (s-flow) were tested ex vivo to validate critical results from the animal model. Results D-flow induced arterial stiffening through collagen deposition after partial carotid ligation, and the degree of stiffening was similar to that of unmanipulated carotid arteries from 80-week-old mice. Intimal gene pathway analyses identified that transforming growth factor-beta (TGF-β) pathways having a prominent role in this stiffened arterial response, but that this was due to thrombospondin-1 (TSP-1) stimulation of profibrotic genes and not changes to TGF- β. In vitro and in vivo testing under d-flow conditions identified a possible role for TSP-1 activation of TGF-β in the upregulation of these genes. TSP-1 knockout animals had significantly less arterial stiffening in response to d-flow than wild type carotid arteries. Human arteries exposed to d-flow had similar increases TSP-1 and collagen gene expression as seen in our model. Conclusions TSP-1 has a critical role in shear-mediated arterial stiffening that is mediated in part through TSP-1’s activation of TGF-β’s profibrotic signaling pathways. Molecular targets in this pathway may lead to novel therapies to limit arterial stiffening and the progression of disease in arteries exposed to d-flow.

Pelvic organ prolapse is characterized as the descent of the pelvic organs into the vaginal canal. In the USA, there is a 12% lifetime risk for requiring surgical intervention. Although vaginal childbirth is a well-established risk factor for prolapse, the underlying mechanisms are not fully understood. Decreased smooth muscle organization, composition and maximum muscle tone are characteristics of prolapsed vaginal tissue. Maximum muscle tone of the vaginal wall was previously investigated in the circumferential or axial direction under uniaxial loading; however, the vaginal wall is subjected to multiaxial loads. Further, the contribution of vaginal smooth muscle basal (resting) tone to mechanical function remains undetermined. The objectives of this study were to determine the contribution of smooth muscle basal and maximum tone to the regional biaxial mechanical behaviour of the murine vagina. Vaginal tissue from C57BL/6 mice was subjected to extension–inflation protocols ( n = 10) with and without basal smooth muscle tone. Maximum tone was induced with KCl under various circumferential ( n = 5) and axial ( n = 5) loading conditions. The microstructure was visualized with multiphoton microscopy ( n = 1), multiaxial histology ( n = 4) and multiaxial immunohistochemistry ( n = 4). Smooth muscle basal tone decreased material stiffness and increased anisotropy. In addition, maximum vaginal tone was decreased with increasing intraluminal pressures. This study demonstrated that vaginal muscle tone contributed to the biaxial mechanical response of murine vaginal tissue. This may be important in further elucidating the underlying mechanisms of prolapse, in order to improve current preventative and treatment strategies.

Cephalopelvic disproportion (CPD)-related obstructed labor is accountable for 3–8% of the maternal deaths worldwide. The consequence of CPD-related obstructive labor in the absence of a Caesarian section (C/S) is often maternal or perinatal mortality or morbidity to the mother and/or the infant. Accurate and timely referral of at-risk mothers to health facilities where C/S is a delivery option could reduce maternal mortality in the developing world. The goal of this work was to develop and test the feasibility of a safe, low-cost, easy-to-use, portable tool, using a Microsoft Kinect 3D camera, to identify women at risk for obstructed labor due to CPD. Magnetic resonance imaging (MRI) scans, 3D camera imaging, anthropometry and clinical pelvimetry were collected and analyzed from women 18–40 years of age, at gestational age ≥36+0 weeks with previous C/S due to CPD (n = 43), previous uncomplicated vaginal deliveries (n = 96), and no previous obstetric history (n = 148) from Addis Ababa, Ethiopia. Novel and published CPD risk scores based on anthropometry, clinical pelvimetry, MRI, and Kinect measurements were compared. Significant differences were observed in most anthropometry, clinical pelvimetry, MRI and Kinect measurements between women delivering via CPD-related C/S versus those delivering vaginally. The area under the receiver-operator curve from novel CPD risk scores base on MRI-, Kinect-, and anthropometric-features outperformed novel CPD risk scores based on clinical pelvimetry and previously published indices for CPD risk calculated from these data; e.g., pelvic inlet area, height, and fetal-pelvic index. This work demonstrates the feasibility of a 3D camera-based platform for assessing CPD risk as a novel, safe, scalable approach to better predict risk of CPD in Ethiopia and warrants the need for further blinded, prospective studies to refine and validate the proposed CPD risk scores, which are required before this method can be applied clinically.

Background: Healthy function of tricuspid valve (TV) structures is essential to avoid tricuspid regurgitation (TR) and may significantly improve disease prognosis. Mitral valve (MV) structures have been extensively studied, but little is known about the TV and right-sided heart diseases. Therefore, clinical decisions and finite element (FE) simulations often rely heavily on MV data for TV applications, despite fundamentally different mechanical and physiological environments. Method/Results: To bridge this gap, we performed a rigorous mechanical, morphological, and microstructural characterization of the MV and TV leaflets and chordae in a porcine model. Planar biaxial testing, uniaxial testing, second harmonic generation imaging and Verhoeff Van Gieson staining were performed. Morphological parameters, tissue moduli, extensibility, and anisotropy were quantified and compared. No major differences in leaflet mechanics or structure were found between TV and MV; chordal mechanics, morphology, and structure were found to compensate for anatomical and physiological loading differences between the valves. No differences in chordal mechanics were observed by insertion point within a leaflet; the septal tricuspid leaflet (STL) and posterior mitral leaflet (PML) did not have distinguishable strut chords, and the STL had the shortest chords. Within a valve, chords from septally-located leaflets were more extensible. MV chords were stiffer. Conclusions: This study presents the first rigorous comparative mechanical and structural dataset of MV and TV structures. Valve type and anatomical location may be stronger predictors of chordal mechanics. Chords from septally-located leaflets differ from each other and from their

Background: Marfan syndrome (MFS), a genetic disorder of the connective tissue, has been strongly linked to dilation of the thoracic aorta, among other cardiovascular complications. As a result, MFS patients frequently suffer from aortic dissection and rupture, contributing to the high rate of mortality and morbidity among MFS patients. Despite the significant effort devoted to the investigation of mechanical and structural properties of aneurysmal tissue, studies on Marfan aneurysmal biomechanics are scarce. Ex vivo mechanical characterization of MFS aneurysmal tissue can provide a better insight into tissue strength outside the physiologic loading range and serve as a basis for improved risk assessment and failure prediction. Methods:The mechanical and microstructural properties of MFS aneurysmal thoracic aorta (MFS, n=15, 39.5±3.91 years), non-MFS aneurysmal thoracic aorta (TAA, n=8, 52.8±4.9 years), healthy human thoracic aorta (HH, n=8, 75.4±6.1 years), and porcine thoracic aorta (n=10) are investigated. Planar biaxial tensile testing and uniaxial failure testing were utilized to characterize the mechanical and failure properties of the tissue, respectively. Verhoeff-Van Gieson (VVG) and PicroSirius Red stains were utilized to visualize the elastin and collagen fiber architecture, respectively.Results: MFS tissue was found to have age-dependent but diameter-independent mechanical, structural, and morphological properties, also showing extensive elastin fiber degradation. Non-MFS thoracic aneurysmal aorta was thicker and stiffer than age-matched MFS tissue. Moreover, non-MFS thoracic aneurysmal mechanics resembled closely the mechanics of older healthy human tissue. Younger MFS tissue (<40 years) exhibited similar mechanical and structural properties to aged porcine tissue.Conclusions: Both age and aneurysmal presence were found to be factors associated with increased stiffness in aortic tissue, and aortic diameter was not a significant determinant of mechanical property deterioration. Additionally, the presence of MFS was found to induce stiffening of the thoracic aorta, although not to the extent of the non-MFS aneurysm.

Activation of the nuclear hormone receptor, PPARγ, with pharmacological agonists promotes a contractile vascular smooth muscle cell phenotype and reduces oxidative stress and cell proliferation, particularly under pathological conditions including vascular injury, restenosis, and atherosclerosis. However, pharmacological agonists activate both PPARγ-dependent and -independent mechanisms in multiple cell types confounding efforts to clarify the precise role of PPARγ in smooth muscle cell structure and function in vivo. We, therefore, designed and characterized a mouse model with smooth muscle cell-targeted PPARγ overexpression (smPPARγOE). Our results demonstrate that smPPARγOE attenuated contractile responses in aortic rings, increased aortic compliance, caused aortic dilatation, and reduced mean arterial pressure. Molecular characterization revealed that compared to littermate control mice, aortas from smPPARγOE mice expressed lower levels of contractile proteins and increased levels of adipocyte-specific transcripts. Morphological analysis demonstrated increased lipid deposition in the vascular media and in smooth muscle of extravascular tissues. In vitro adenoviral-mediated PPARγ overexpression in human aortic smooth muscle cells similarly increased adipocyte markers and lipid uptake. The findings demonstrate that smooth muscle PPARγ overexpression disrupts vascular wall structure and function, emphasizing that balanced PPARγ activity is essential for vascular smooth muscle homeostasis.

year 2 (relative risk, 0.98; 95% CI, 0.95-1.01), or year 3 (relative risk, 0.99; 95% CI, 0.96-1.03). This association was consistent for patients undergoing EVAR, LEB or PVI, and CEA or CAS procedures.Comments: This study combines two very large data sets to help determine if practice patterns are altered by being part of a national quality improvement registry. The answer is that it does not at the current time. As scrutiny of the results included in the quality data by external agents or individuals within the quality registry becomes the norm, this may well change and has as exemplified by some of the more mature quality groups (New England Collaborative). Patient education (patient's know that monitoring is essential), common guidelines across specialties, and simplified surveillance modalities (ultrasound rather than CT) are three strategies the authors' feel may aid in better surveillance in the future. No matter the strategies, without having a quality database to benchmark the effect of change little will be gained. The two databases used in this study were appropriate, the Center for Medicare Services (CMS) is the one pushing reimbursement for quality care and the majority of our patients are Medicare participants.

Patient 1 exhibited a more anisotropic mechanical response than Patient 2, with sample stiffness on par with that of adult PV tissue. Additionally, both samples showed radial and circumferential alignment of collagen fibers on the ventricularis and fibrosa sides of the leaflets, respectively. Collagen fibers on the fibrosa side were also more crimped than on the ventricularis side.