Beta-arrestins regulate atherosclerosis and neointimal hyperplasia by controlling smooth muscle cell proliferation and migration.

Atherosclerosis and arterial injury-induced neointimal hyperplasia involve medial smooth muscle cell (SMC) proliferation and migration into the arterial intima. Because many 7-transmembrane and growth factor receptors promote atherosclerosis, we hypothesized that the multifunctional adaptor proteins beta-arrestin1 and -2 might regulate this pathological process. Deficiency of beta-arrestin2 in ldlr(-/-) mice reduced aortic atherosclerosis by 40% and decreased the prevalence of atheroma SMCs by 35%, suggesting that beta-arrestin2 promotes atherosclerosis through effects on SMCs. To test this potential atherogenic mechanism more specifically, we performed carotid endothelial denudation in congenic wild-type, beta-arrestin1(-/-), and beta-arrestin2(-/-) mice. Neointimal hyperplasia was enhanced in beta-arrestin1(-/-) mice, and diminished in beta-arrestin2(-/-) mice. Neointimal cells expressed SMC markers and did not derive from bone marrow progenitors, as demonstrated by bone marrow transplantation with green fluorescent protein-transgenic cells. Moreover, the reduction in neointimal hyperplasia seen in beta-arrestin2(-/-) mice was not altered by transplantation with either wild-type or beta-arrestin2(-/-) bone marrow cells. After carotid injury, medial SMC extracellular signal-regulated kinase activation and proliferation were increased in beta-arrestin1(-/-) and decreased in beta-arrestin2(-/-) mice. Concordantly, thymidine incorporation and extracellular signal-regulated kinase activation and migration evoked by 7-transmembrane receptors were greater than wild type in beta-arrestin1(-/-) SMCs and less in beta-arrestin2(-/-) SMCs. Proliferation was less than wild type in beta-arrestin2(-/-) SMCs but not in beta-arrestin2(-/-) endothelial cells. We conclude that beta-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and that these SMC activities are regulated reciprocally by beta-arrestin2 and beta-arrestin1. These findings identify inhibition of beta-arrestin2 as a novel therapeutic strategy for combating atherosclerosis and arterial restenosis after angioplasty

Rational Misbehavior? Evaluating an Integrated Dual-Process Model of Criminal Decision Making

Objectives: Test the hypothesis that dispositional self-control and morality relate to criminal decision making via different mental processing modes, a 'hot' affective mode and a 'cool' cognitive one. Methods: Structural equation modeling in two studies under separate samples of undergraduate students using scenarios describing two different types of crime, illegal downloading and insurance fraud. Both self-control and morality are operationalized through the HEXACO model of personality (Lee and Ashton in Multivariate Behav Res 39(2):329-358, 2004).Results: In Study 1, negative state affect, i.e., feelings of fear and worry evoked by a criminal prospect, and perceived risk of sanction were found to mediate the relations between both dispositions and criminal choice. In Study 2, processing mode was manipulated by having participants rely on either their thinking or on their feelings prior to deciding on whether or not to make a criminal choice. Activating a cognitive mode strengthened the relation between perceived risk and criminal choice, whereas activating an affective mode strengthened the relation between negative affect and criminal choice.Conclusion: In conjunction, these results extend research that links stable individual dispositions to proximal states that operate in the moment of decision making. The results also add to dispositional perspectives of crime by using a structure of personality that incorporates both self-control and morality. Contributions to the proximal, state, perspectives reside in the use of a new hot/cool perspective of criminal decision making that extends rational choice frameworks. © 2013 Springer Science+Business Media New York