Brant E Isakson

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Apoptotic cells release 'find-me' signals at the earliest stages of death to recruit phagocytes. The nucleotides ATP and UTP represent one class of find-me signals, but their mechanism of release is not known. Here, we identify the plasma membrane channel pannexin 1 (PANX1) as a mediator of find-me signal/nucleotide release from apoptotic cells.(More)
RATIONALE Macrophages change their phenotype and biological functions depending on the microenvironment. In atherosclerosis, oxidative tissue damage accompanies chronic inflammation; however, macrophage phenotypic changes in response to oxidatively modified molecules are not known. OBJECTIVE To examine macrophage phenotypic changes in response to oxidized(More)
Previous studies investigating the role of smooth muscle cells (SMCs) and macrophages in the pathogenesis of atherosclerosis have provided controversial results owing to the use of unreliable methods for clearly identifying each of these cell types. Here, using Myh11-CreER(T2) ROSA floxed STOP eYFP Apoe(-/-) mice to perform SMC lineage tracing, we find that(More)
Cellular interaction in blood vessels is maintained by multiple communication pathways, including gap junctions. They consist of intercellular channels ensuring direct interaction between endothelial and smooth muscle cells and the synchronization of their behavior along the vascular wall. Gap-junction channels arise from the docking of two hemichannels or(More)
Intercellular channels formed by connexin proteins play a pivotal role in the direct movement of ions and larger cytoplasmic solutes between vascular endothelial cells, between vascular smooth muscle cells, and between endothelial and smooth muscle cells. Multiple genetic and epigenetic factors modulate connexin expression levels and/or channel function,(More)
AIMS Pannexins (Panx) form ATP release channels and it has been proposed that they play an important role in the regulation of vascular tone. However, distribution of Panx across the arterial vasculature is not documented. METHODS We tested antibodies against Panx1, Panx2 and Panx3 on human embryonic kidney cells (which do not endogenously express Panx(More)
Gap junctions are common features in the vasculature, long thought to provide a pathway for cell-cell signaling. Emerging understanding of the gap-junctional proteins (connexins) and new tools for their investigation now offer the opportunity to explore the vital role that the gap junctions may play in cardiovascular homeostasis and pathophysiology.
Models of unregulated nitric oxide (NO) diffusion do not consistently account for the biochemistry of NO synthase (NOS)-dependent signalling in many cell systems. For example, endothelial NOS controls blood pressure, blood flow and oxygen delivery through its effect on vascular smooth muscle tone, but the regulation of these processes is not adequately(More)
Inositol (1,4,5)-trisphosphate [Ins(1,4,5)P(3)] originating in the vascular smooth-muscle cells (VSMCs) has been shown to modulate the Ca(2+) stores in endothelial cells (ECs). However, the reverse is not found, suggesting that Ins(1,4,5)P(3) movement might be unidirectional across gap junctions at the myoendothelial junction (MEJ), or that distribution of(More)
OBJECTIVE To determine whether S-nitrosylation of connexins (Cxs) modulates gap junction communication between endothelium and smooth muscle. METHODS AND RESULTS Heterocellular communication is essential for endothelium control of smooth muscle constriction; however, the exact mechanism governing this action remains unknown. Cxs and NO have been(More)