Role of RhoA and Rho-associated kinase in phenotypic switching of vascular smooth muscle cells: Implications for vascular function.

Cardiovascular disease (CVD) continues to be the primary cause of global mortality. Vascular smooth muscle cells (VSMCs) are integral components of vascular structure and function, evident by their vital roles in modulating blood flow and pressure. Such roles exist due to the differentiated contractile phenotype of VSMCs. However, VSMCs may switch to a dedifferentiated, proliferative synthetic phenotype in a phenomenon known as phenotypic switching. This switch involves dramatic changes in VSMC migration, proliferation, gene expression programs, differentiation, cellular stiffness and extracellular matrix (ECM) deposition. In this review, we explore the role of the small GTPase Rho and its effector, Rho-associated kinase (ROCK), in phenotypic switching as well as apoptotic pathways in VSMCs. We critically dissect how RhoA promotes cell migration and proliferation as well as its role in modulating the expression of a battery of VSMC marker proteins. We also discuss how RhoA modulates apoptosis, induces dedifferentiation, increases vascular stiffness, or modifies ECM accumulation. These alterations in VSMC phenotypes contribute to multiple vascular dysfunctions, including hypertension and atherosclerosis. Understanding the molecular underpinnings and the signaling pathways involved in these altered phenotypes may provide novel avenues of drug design and other therapeutic interventions for the management of CVDs.

Sleep pattern and predictors of daily versus as-needed hypnotics use in middle-aged and older adults with insomnia.

INTRODUCTION: This study aims to examine the sleep pattern and predictors of daily vs. as-needed use of hypnotics in middle-aged and older adults with insomnia. METHODS: Patients aged 50-75 who use hypnotics for insomnia were identified via electronic medical records and were recruited. Data about sociodemographics, mood and cognitive screening measures, and questions related to sleep patterns were collected through an interview conducted over the phone. RESULTS: A sample of 66 participants was recruited, of which 69.7% were females. Three quarters (49/66, 74.2%) used hypnotics daily, with 43% (21/49) of daily hypnotics users sleeping more than 8 h per night. Two-fifths (26/66, 39.4%) of participants still had clinically significant insomnia even after taking hypnotics. After adjusting for age, years of hypnotics use, sleeping hours per night, PHQ-2 score, and frequency of pain at night, the logistic regression model showed that younger age (p = 0.023) and longer sleeping hours per night (p = 0.025) were significantly associated with daily hypnotics use when compared to as needed hypnotics use. CONCLUSION: Many hypnotic users still have clinically significant insomnia and poor quality of sleep as reflected by perceived longer sleep duration and more daytime napping which could be related to drug-related residual sedation. Hypnotic use may not be the best solution for insomnia treatment in an older population, and physicians should regularly reassess the use of hypnotics.