Elastogenesis Correlates With Pigment Production in Murine Aortic Valve Leaflets

Objective: Aortic valve (AV) leaflets rely on a precise extracellular matrix (ECM) microarchitecture for appropriate biomechanical performance. The ECM structure is maintained by valvular interstitial cells (VICs), which reside within the leaflets. The presence of pigment produced by a melanocytic population of VICs in mice with dark coats has been generally regarded as a nuisance, as it interferes with histological analysis of the AV leaflets. However, our previous studies have shown that the presence of pigment correlates with increased mechanical stiffness within the leaflets as measured by nanoindentation analyses. In the current study, we seek to better characterize the phenotype of understudied melanocytic VICs, explore the role of these VICs in ECM patterning, and assess the presence of these VICs in human aortic valve tissues.Approach and Results: Immunofluorescence and immunohistochemistry revealed that melanocytes within murine AV leaflets express phenotypic markers of either neuronal or glial cells. These VIC subpopulations exhibited regional patterns that corresponded to the distribution of elastin and glycosaminoglycan ECM proteins, respectively. VICs with neuronal and glial phenotypes were also found in human AV leaflets and showed ECM associations similar to those observed in murine leaflets. A subset of VICs within human AV leaflets also expressed dopachrome tautomerase, a common melanocyte marker. A spontaneous mouse mutant with no aortic valve pigmentation lacked elastic fibers and had reduced elastin gene expression within AV leaflets. A hyperpigmented transgenic mouse exhibited increased AV leaflet elastic fibers and elastin gene expression.Conclusions: Melanocytic VIC subpopulations appear critical for appropriate elastogenesis in mouse AVs, providing new insight into the regulation of AV ECM homeostasis. The identification of a similar VIC population in human AVs suggests conservation across species.

A Single-Center Trial to Evaluate the Efficacy and Tolerability of Four Microneedling Treatments on Fine Lines and Wrinkles of Facial and Neck Skin in Subjects With Fitzpatrick Skin Types I-IV: An Objective Assessment Using Non-Invasive Devices and 0.33mm Microbiopsies

Background While ablative techniques have been standard of care for the treatment of fine lines and wrinkles, microneedling is a minimally invasive alternative. Objectives The purpose of this study was to assess the efficacy of microneedling on facial and neck fine lines and wrinkles. Methods 35 subjects between 44 and 65 years old with Fitzpatrick skin types I-IV received four monthly microneedling treatments over the face and neck. Subjects returned one and three months post-treatment. At every visit, high-resolution ultrasonography, optical coherence tomography, transepidermal water loss and BTC-2000 were performed. 0.33mm microbiopsies were collected pre-treatment, before the fourth treatment and three months post-treatment. Results 32 subjects (93.75% female, 6.25% male) completed all seven visits. Facial dermal and epidermal density increased 101.86% and 19.28%, respectively from baseline at three months post-treatment. Facial elasticity increased 28.2% from baseline three months post-treatment. Facial attenuation coefficient increased 15.65% and 17.33% one and three months post-treatment. At study completion, blood flow 300µm deep decreased 25.8% in the face and 42.3% in the neck. Relative collagen type III and elastin gene expression was statistically higher three months post-treatment. However, total elastin protein levels unchanged compared to baseline. 58% of biopsies extracted three months post-treatment showed dermal muscle formation, compared to baseline 15.3%. Conclusions The results illustrate the effects of microneedling treatments. Non-invasive measurements and biopsy data showed changes in skin architecture and collagen/elastin gene expression suggesting skin rejuvenation, with new extracellular matrix production and muscle formation.

4′,7-Isoflavandiol (Equol) Enhances Human Dermal Fibroblast Renewal and Has Effects Similar to 17β-Estradiol in Stimulating Collagen and Elastin Expression. Cell Cycle and RT-PCR Analysis without Phenol Red

Polyphenols have general health benefits including anti-photoaging influences to counter the negative effects of ultra-violet (UV) rays from solar light (via the generation of reactive oxygen species (ROS) and oxidative stress (OS)), which leads to the stimulation of matrix metalloproteinases (MMPs) that break down collagen and elastin. The changes in elastin and collagen represent major factors in dermal aging along with a decrease in skin fibroblast number and function. The purpose of this study was to determine the influence of a polyphenolic molecule, 4′,7-Isoflavandiol (Equol) at 10 nM on: (1) fibroblast number and function via cell cycle testing (including apoptosis) and collagen protein expression (types I and III) using long-term (eight-week) 3D human fibroblast cultures by intracellular fluorescent-activated cell sorting (FACS) analysis, and (2) quantifying elastin gene expression levels in short-term (four day) cultures using human monolayer fibroblasts by RT-PCR. In both in vitro testing methods, the presence of phenol red (tissue culture indicator) interfered with the parameter results. Therefore, all experiments were performed without phenol red. Using FACS analysis in the long-term 3D cultures exposure to 10 nM of equol for four days significantly increased the percentage of cycling fibroblasts (rejuvenation) above vehicle control (dimethyl sulfoxide (DMSO)) or 17β-estradiol levels, while apoptosis was not altered by any treatment. In addition, in the long-term cultures, collagen levels were significantly increased in the equol and 17β-estradiol treatments above vehicle control values. In short-term cultures, 10 nM of equol or 17β-estradiol significantly increased elastin gene expression levels above vehicle control values. In summary: (a) phenol red may interfere with tissue culture parameter results and (b) the polyphenolic equol compound, derived from plants, may provide protection against photoaging in cosmetic formulations by stimulating collagen, elastin, and enhancing fibroblast renewal.

Tympanic Membrane Retractions in patients with Williams Syndrome: A Controlled Study

Introduction The role of elastin in tympanic retractions and chronic otitis media is not well established. Williams Syndrome (WS), a pathology related to a mutation in the elastin gene, could generate tympanic retractions. Objective To compare the prevalence of tympanic retractions among patients with WS and controls. Methods WS patients (n = 43 ears) and controls (n = 130 ears) were evaluated by digital otoscopic examination and the degree of tympanic membrane retraction was classified by 2 blinded experienced otolaryngologists. Results The agreement rate between the evaluators was 71.1% for pars tensa and 65% for pars flaccida retraction (p < 0.001). The pars tensa and pars flaccida retractions are present in patients with WS after an adjusted residue of respectively - 2.8 and - 2.6 (p = 0.011 and p = 0.022) compared with controls. Conclusions Tympanic membrane retractions are not more common in the WS group when compared with controls.

Antibacterial polymer nanofiber-coated and high elastin protein-expressing BMSCs incorporated polypropylene mesh for accelerating healing of female pelvic floor dysfunction

To solve the bio-inertness of widely used polypropylene (PP) mesh for treating pelvic floor dysfunction (PFD), a novel strategy of incorporation with elastin gene-transfected bone marrow stem cells (BMSCs) and antibacteria drug-loaded polylactic acid (PLA) nanofibrous mat covering layer was proposed to overcome the limitation of the pristine PP mesh. Then, a series of physicochemical and in vitro experiments were applied to investigate the improvement of the as-prepared material. The elastin protein expression was proved to be upregulated without obvious cytotoxicity influence after the gene transfection and also improved the cell migration rate. In addition, the antibacteria drug-loaded PLA nanofibrous mat on the PP mesh could efficiently inhibit bacteria and showed no significant impact on cell adhesion and proliferation. Thus, we believe that the incorporation of the elastin gene-transfected BMSCs and nanofiber-coated PP mesh would be a potential candidate in the application of female PFD.

Sedation in a patient with William Syndrome without supravalvular aortic stenosis and normal QT: Challenge still remains

William Syndrome (WS) is a rare genetic condition related to deletion of elastin gene resulting in distinctive facies, cardiovascular diseases, learning difficulties, developmental delay, unique personality characteristics, endocrine involvement, etc.1 Although successful anaesthesia is reported, literature review indicate significant major adverse cardiac events (MACE) including sudden death, as frequent.2 So anaesthetic management of these patients has proved to be challenging. The cardiovascular abnormality, corrected QT, and cardio-depressant actions of anaesthetic drugs need critical considerations.

Severe Mitral Valve Regurgitation due to Significant Coronary Artery Stenosis in a 14-month-old boy with Williams-Beuren Syndrome

IntroductionWilliams-Beuren syndrome (WBS) is characterized by a combination of cardiovascular malformations, typical dysmorphic stigmata, a moderate developmental delay and behavioral abnormalities. According to the literature the incidence is within a range from 1:20 000 to 1:7 500 (Yildiz O et al., World J Pediatr Congenit Heart Surg 2015; 6: 311–316). Microdeletion of chromosome region 7q11.23 is pathognomonic, affecting the elastin gene (von Beust G et al., Klin Padiatr 2000; 212: 299–307). Due to reduced elastin content elasticity in the media of the arterial vessel wall is reduced, resulting in a vasculopathy affecting preferentially the medium size and large arteries. As a characteristic feature supravalvular aortic and pulmonary artery stenosis is very common in patients with WBS. The supravalvular aortic stenosis may also affect the origin of the coronary arteries resulting in an increased risk of myocardial ischemia (Collins RT 2nd, Circulation 2013; 127: 2125–2134). We report the case of a little boy with ischemic mitral regurgitation due to stenosis of the left main coronary artery.

Williams-Beuren Syndrome

Williams-Beuren syndrome, also known as Williams syndrome (WS) is a genetic disorder involving the elastin gene on chromosome 7q11.23. Elastin is important for elasticity of vascular walls, and its deficiency can lead to widespread arteriopathy, most notably supravalvar aortic stenosis of the ascending aorta and coronary artery stenosis. Because of these cardiac defects, patients with WS are at high risk for cardiac arrest under anesthesia with a documented incidence around 5%. Appropriate perioperative management of all anesthetics includes a multidisciplinary approach to risk stratification, precise anesthetic management, and disaster planning. This chapter reviews the etiology, pathogenesis, diagnosis, and manifestations of WS. The authors also discuss the preoperative workup and anesthetic implications of WS, as well as issues related to cardiac arrest and extracorporeal cardiopulmonary resuscitation.