Vascular smooth muscle cell plasticity plays a pivotal role in the pathophysiology of vascular diseases. Despite compelling evidence demonstrating the importance of transcription factor GATA6 in vascular smooth muscle, the functional role of GATA6 remains poorly understood. The aim of this study was to elucidate the role of GATA6 on cell migration and to gain insight into GATA6-sensitive genes in smooth muscle. We found that overexpression of GATA6 promotes migration of human coronary artery smooth muscle cells in vitro, and that silencing of GATA6 in smooth muscle cells resulted in reduced cellular motility. Furthermore, a complete microarray screen of GATA6-sensitive gene transcription resulted in 739 upregulated and 248 downregulated genes. Pathways enrichment analysis showed involvement of transforming growth factor beta (TGF-β) signaling which was validated by measuring mRNA expression level of several members. Furthermore, master regulators prediction based on microarray data revealed several members of (mitogen activated protein kinase) MAPK pathway as a master regulators, reflecting involvement of MAPK pathway also. Our findings provide further insights into the functional role of GATA6 in vascular smooth muscle and suggest that targeting GATA6 may constitute as a new approach to inhibit vascular smooth muscle migration.

Background: Hypertension remains a major risk factor for cardiovascular diseases, but the underlying mechanisms are not well understood. We hypothesize that appropriate mechanotransduction and contractile function in vascular smooth muscle cells are crucial to maintain vascular wall integrity. The Hippo pathway effectors YAP (yes-associated protein 1) and TAZ (WW domain containing transcription regulator 1) have been identified as mechanosensitive transcriptional coactivators. However, their role in vascular smooth muscle cell mechanotransduction has not been investigated in vivo. Methods: We performed physiological and molecular analyses utilizing an inducible smooth muscle–specific YAP/TAZ knockout mouse model. Results: Arteries lacking YAP/TAZ have reduced agonist-mediated contraction, decreased myogenic response, and attenuated stretch-induced transcriptional regulation of smooth muscle markers. Moreover, in established hypertension, YAP/TAZ knockout results in severe vascular lesions in small mesenteric arteries characterized by neointimal hyperplasia, elastin degradation, and adventitial thickening. Conclusions: This study demonstrates a protective role of YAP/TAZ against hypertensive vasculopathy.

Aortic aneurysms are defined as an irreversible increase in arterial diameter by more than 50% relative to the normal vessel diameter. The incidence of aneurysm rupture is about 10 in 100,000 persons per year and ruptured arterial aneurysms inevitably results in serious complications, which are fatal in about 40% of cases. There is also a hereditary component of the disease and dilation of the ascending thoracic aorta is often associated with congenital heart disease such as bicuspid aortic valves (BAV). Furthermore, specific mutations that have been linked to aneurysm affect polymerization of actin filaments. Polymerization of actin is important to maintain a contractile phenotype of smooth muscle cells enabling these cells to resist mechanical stress on the vascular wall caused by the blood pressure according to the law of Laplace. Interestingly, polymerization of actin also promotes smooth muscle specific gene expression via the transcriptional co-activator MRTF, which is translocated to the nucleus when released from monomeric actin. In addition to genes encoding for proteins involved in the contractile machinery, recent studies have revealed that several non-coding microRNAs (miRNAs) are regulated by this mechanism. The importance of these miRNAs for aneurysm development is only beginning to be understood. This review will summarize our current understanding about the influence of smooth muscle miRNAs and actin polymerization for the development of arterial aneurysms.

Introduction: In this article are demonstrated differences in the aspects of the metabolic syndrome (MSy) between genders, as well as the association of MSy and neuropathy. The aim: The aim of our study was that in patients with newly discovered metabolic syndrome of both sexes make comparison of fasting blood glucose levels and after oral glucose tolerance test, as well as neurophysiological parameters of n.medianus and n.ulnaris. Patients and methods: All participants were examined dermatologically. The analysis included the 36 male and 36 female respondents with a newly discovered MSy. Results: The average age of men was 52.75±7.5 (40-65) years and women 52.1±7.7 (38-67) years. The average value of fasting blood glucose in women was 5.86±0.87 (4.5-8) mmol/L, and non significantly higher in men (p=0.0969) as 6.19±0.8 (4.7-8) mmol/L. Average values of blood sugar 120 minutes after oral glucose tolerance test were not significantly different (p=0.7052), and was 5.41±1.63 (3.3-9.7) mmol/L in women and 5.27±1.52 (2.7-9.8) mmol/L in men. Median motor velocity were significantly higher in women for n.medianus on the left (p=0.0024), n.ulnaris on the left (p=0.0081) and n.ulnaris on the right side (p=0.0293), and the median motor terminal latency were significantly longer in n.ulnaris on the left (p=0.0349) and n.ulnaris on the right side (p=0.011). There was no significant difference in the sensory conductivity velocity in n.medianus and n.ulnaris between the groups, but the amplitude with the highest peak of the sensory response was significantly higher in n.medianus on the left (p=0.0269) and n.ulnaris on the left side (p=0.0009) in female patients. Conclusion: The results indicate that there are differences in neurophysiological parameters of the investigated nerves between the genders, and that tested nerve structures in the course of MSy are affected slightly more in men. There were no significant differences in skin changes between genders.