We have provided evidence that microvascular abnormalities such as vascular rarefaction can cause an increase in peripheral resistance and might initiate the pathogenic sequence in hypertension. In addition, shared insulin-signaling pathways in metabolic and vascular target tissues may provide a mechanism to couple the regulation

of glucose and hemodynamic homeostasis. Metabolic insulin resistance is characterized Crenolanib molecular weight by pathway-specific impairment in PI3K-dependent signaling, which, in endothelium, may cause imbalance between production of NO and secretion of ET-1, limiting nutritive blood flow, and thus insulin and substrate delivery to target tissues, and possibly increasing vascular resistance. Adipose tissue-derived FFAs, upregulated RAS, pro-inflammatory cytokines including TNF-α, as well as decreased adiponectin expression, may contribute to impairment of insulin’s Gefitinib nmr metabolic and vascular actions by modulating insulin signaling and transcription. Perivascular and truncal fat adipose tissue act as an integrated organ responsible for generating these local and systemic signals. The current studies focusing on adipose tissue derived cytokines

and their modulating effects on microvascular function, promise a better understanding of the pathophysiology underlying the clustering of cardiovascular risk factors. These results may lead to new therapeutic approaches that specifically target underlying causes of obesity-related disorders. “
“Please cite this paper as: LeBlanc AJ, Krishnan L, Sullivan CJ, Williams SK, Hoying JB. Microvascular repair: post-angiogenesis vascular dynamics. Microcirculation19: 676–695, 2012. Vascular compromise and the accompanying perfusion

deficits cause or complicate a large array of disease conditions and treatment failures. This has prompted the exploration of therapeutic strategies to repair or regenerate vasculatures, thereby establishing more competent microcirculatory beds. Growing evidence indicates that Sinomenine an increase in vessel numbers within a tissue does not necessarily promote an increase in tissue perfusion. Effective regeneration of a microcirculation entails the integration of new stable microvessel segments into the network via neovascularization. Beginning with angiogenesis, neovascularization entails an integrated series of vascular activities leading to the formation of a new mature microcirculation, and includes vascular guidance and inosculation, vessel maturation, pruning, AV specification, network patterning, structural adaptation, intussusception, and microvascular stabilization. While the generation of new vessel segments is necessary to expand a network, without the concomitant neovessel remodeling and adaptation processes intrinsic to microvascular network formation, these additional vessel segments give rise to a dysfunctional microcirculation.