Moderate alcohol consumption targets S100β+ vascular stem cells and attenuates injury-induced neointimal hyperplasia

Background Stem cells present in the vessel wall may be triggered in response to injurious stimuli to undergo differentiation and contribute to vascular disease development. Our aim was to determine the effect of moderate alcohol (EtOH) exposure on the expansion and differentiation of S100 calcium-binding protein B positive (S100β+) resident vascular stem cells and their contribution to pathologic vessel remodeling in a mouse model of arteriosclerosis. Methods and Results Lineage tracing analysis of S100β+ cells was performed in male and female S100β-eGFP/Cre/ERT2–dTomato transgenic mice treated daily with or without EtOH by oral gavage (peak BAC: 15 mM or 0.07%) following left common carotid artery ligation for 14 days. Carotid arteries (ligated or sham-operated) were harvested for morphological analysis and confocal assessment of fluorescent-tagged S100 β + cells in FFPE carotid cross sections. Ligation-induced carotid remodeling was more robust in males than in females. EtOH-gavaged mice had less adventitial thickening and markedly reduced neointimal formation compared to controls, with a more pronounced inhibitory effect in males compared to females. There was significant expansion of S100β+-marked cells in vessels postligation, primarily in the neointimal compartment. EtOH treatment reduced the fraction of S100β+ cells in carotid cross sections, concomitant with attenuated remodeling. In vitro, EtOH attenuated Sonic Hedgehog-stimulated myogenic differentiation (as evidenced by reduced calponin and myosin heavy chain expression) of isolated murine S100β+ vascular stem cells. Conclusions These data highlight resident vascular S100β+ stem cells as a novel target population for alcohol and suggest that regulation of these progenitors in adult arteries, particularly in males, may be an important mechanism contributing to the antiatherogenic effects of moderate alcohol consumption

Moderate Alcohol Consumption Targets S100β +

BACKGROUND. Stem cells present in the vessel wall may be triggered in response to injurious stimuli to undergo differentiation and contribute to vascular disease development. Our aim was to determine the effect of moderate alcohol (EtOH) exposure on the expansion and differentiation of S100 calcium-binding protein B positive (S100β(+)) resident vascular stem cells and their contribution to pathologic vessel remodeling in a mouse model of arteriosclerosis. METHODS AND RESULTS. Lineage tracing analysis of S100β(+) cells was performed in male and female S100β-eGFP/Cre/ERT2–dTomato transgenic mice treated daily with or without EtOH by oral gavage (peak BAC: 15mM or 0.07%) following left common carotid artery ligation for 14 days. Carotid arteries (ligated or sham-operated) were harvested for morphological analysis and confocal assessment of fluorescent-tagged S100β (+) cells in FFPE carotid cross sections. Ligation-induced carotid remodeling was more robust in males than in females. EtOH-gavaged mice had less adventitial thickening and markedly reduced neo-intimal formation compared to controls, with a more pronounced inhibitory effect in males compared to females. There was significant expansion of S100β (+) marked cells in vessels post-ligation, primarily in the neo-intimal compartment. EtOH treatment reduced the fraction of S100β (+) cells in carotid cross-sections, concomitant with attenuated remodeling. In vitro, EtOH attenuated Sonic Hedgehog-stimulated myogenic differentiation (as evidenced by reduced calponin and myosin heavy chain expression) of isolated murine S100β (+) vascular stem cells. CONCLUSIONS. These data highlight resident vascular S100β (+) stem cells as a novel target population for alcohol, and suggest that regulation of these progenitors in adult arteries, particularly in males, may be an important mechanism contributing to the anti-atherogenic effects of moderate alcohol consumption

A country at war: mass-observation and rural England, 1939–45

The history of the rural areas during the Second World War is virtually unstudied. There is some work on agriculture and agricultural policies, but the extent to which these rely on K.A.H.Murray's ‘official’ history, published in 1955, is testimony both to the quality of Murray's work and the general paucity of more recent published research. Moving away from the directly official, or economic history, we move into the field of memoir and reminiscence. Good as many of these are, they obviously seldom make any attempt at sustained analysis. Crucially, the rural areas have been left out of accounts of the social history of the war, such as Angus Calder's magisterial studyThe People's War, first published in 1971