The Yorkie homologues YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif, also known as WWTR1), effectors of the Hippo pathway, have been identified as mediators for mechanical stimuli. However, the role of YAP/TAZ in haemodynamics-induced mechanotransduction and pathogenesis of atherosclerosis remains unclear. Here we show that endothelial YAP/TAZ activity is regulated by different patterns of blood flow, and YAP/TAZ inhibition suppresses inflammation and retards atherogenesis. Atheroprone-disturbed flow increases whereas atheroprotective unidirectional shear stress inhibits YAP/TAZ activity. Unidirectional shear stress activates integrin and promotes integrin-Gα interaction, leading to RhoA inhibition and YAP phosphorylation and suppression. YAP/TAZ inhibition suppresses JNK signalling and downregulates pro-inflammatory genes expression, thereby reducing monocyte attachment and infiltration. In vivo endothelial-specific YAP overexpression exacerbates, while CRISPR/Cas9-mediated Yap knockdown in endothelium retards, plaque formation in ApoE mice. We also show several existing anti-atherosclerotic agents such as statins inhibit YAP/TAZ transactivation. On the other hand, simvastatin fails to suppress constitutively active YAP/TAZ-induced pro-inflammatory gene expression in endothelial cells, indicating that YAP/TAZ inhibition could contribute to the anti-inflammatory effect of simvastatin. Furthermore, activation of integrin by oral administration of MnCl reduces plaque formation. Taken together, our results indicate that integrin-Gα-RhoA-YAP pathway holds promise as a novel drug target against atherosclerosis.
Rather, ecological variables are necessary to examine structural, contextual, and sociological effects on human behavior and disease development. Schwartz, 1994 b, p. 823 Many attempts have been made to define (e.g., Rohner, 1984) and then to measure culture. Given the classic definition of culture provided by Kroeber and Kluckhohn (1952), this mapping has usually been made by using values. The most widely known value mapping is the work of Hofstede (1980), whose four value dimensions of Individualism-Collectivism, Power Distance, Uncertainty Avoidance, and Masculinity-Femininity are used as organizing and explanatory constructs in many disciplines. Tapping values salient to Chinese people, the Chinese Culture Connection (1987) has identified one additional dimension to the Hofstede four: Confucian Work Dynamism, or short-term versus long-term orientation (Hofstede, 1991). All five dimensions of culture-level values have provided the conceptual impetus for numerous cross-cultural studies. Several major cross-cultural projects have been conducted subsequent to Hofstede's (1980) groundbreaking work. With his theory-derived value survey, Schwartz (1994 a) has identified seven culture-level dimensions, namely, Conservatism, Intellectual Autonomy, Affective Autonomy, Hierarchy, Egalitarian Commitment, Mastery, and Harmony. Smith, Dugan, and Trompenaars (1996) have identified two reliable value dimensions at the cultural level from their analysis of managerial values: Egalitarian Commitment versus Conservatism, and Utilitarian Involvement versus Loyal Involvement. Smith and Bond (1998, Ch. 3) concluded that these different value surveys have produced convergent results, lending support to the validity of the cultural dimensions originally identified by Hofstede (1980). Recently, House and his associates (2003) have orchestrated a major project to identify cultural dimensions across 62 countries. A distinctive feature of this multicultural project is that values associated with leadership were measured concurrently with ideal and actual leadership behaviors. The House team has identified nine culture-level dimensions:
Recently, Leung et al. (2002) have identified a pan‐cultural set of five dimensions tapping beliefs about the world in which each individual functions. These general axioms may be conceptualized as individual assessments of the social context constraining one's behavioural choices. As such, we hypothesize that these beliefs about the world may be combined with measures of motivation to predict an individual's actions. To test this model, the present research examined the usefulness of these social axioms as predictors of behavioural tendencies in conjunction with four comprehensive dimensions of values (Schwartz, 1992). Hierarchical regression analyses showed that social axioms added moderate predictive power over and above that provided by values to vocational choices, methods of conflict resolution, and coping styles. Specifically, reward for application was related to preference for conventional jobs and accommodation in conflict resolution; religiosity was related to accommodation and to competition in conflict resolution; social cynicism was related negatively to collaboration and to compromise in conflict resolution, and positively to wishful thinking in coping; fate control was related positively to wishful thinking and distancing in coping; and social complexity was related to compromise and to collaboration in conflict resolution, and to problem‐solving as a coping strategy. It thus seems as if measures of respondents' beliefs about the external, social world supplement measures of their internal motivations to achieve various goals. Copyright © 2004 John Wiley & Sons, Ltd.
Background In the face of the global pandemic of coronavirus disease‐2019 (COVID‐19), people’s adherence to precautionary behavioral measures (e.g. social distancing) largely influences the effectiveness of those measures in containing the spread of the coronavirus. The present study aims at testing the applicability of the health belief model (HBM) and generalised social beliefs (i.e. social axioms) to explore strategies for promoting adherence to COVID‐19 precautionary measures. Methods We conducted a telephone survey with a two‐step stratified random sampling method and obtained a probability sample of 616 adults in Macao, China (18–87 years old; 60.9% women) in April 2020. Results Our participants showed stronger adherence to some COVID‐19 precautionary measures (e.g. face mask wearing; 96.4%) but not others (e.g. social distancing; 42.3%). Their adherence to those measures was found to be significantly associated with four HBM factors and two social axioms, after controlling for gender, age, and years of education. Conclusions The HBM and the generalised social beliefs of social cynicism and reward for application can be applied to understanding adherence to precautionary measures against COVID‐19. Strategies based on beliefs were proposed to facilitate the promotion of precautionary measures.
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