Genetic heterogeneity of skin microvasculature

Abstract

Angiogenesis, the formation of new blood vessels from existing vasculature, is a complex process that is essential for normal embryonic development. Current models for experimental evaluation of angiogenesis often use tissue from large vessels like the aorta and umbilical vein, which are phenotypically distinct from microvasculature. We demonstrate that the utilization of skin to measure microvascular angiogenesis in embryonic and adult tissues is an efficient way to quantify microvasculature angiogenesis. We validate this approach and demonstrate its added value by showing significant differences in angiogenesis in monogenic and polygenic mouse models. We discovered that the pattern of angiogenic response among inbred mouse strains in this ex vivo assay differ from the strain distributions of previous in vivo angiogenesis assays. The difference between the ex vivo and in vivo assays may be related to systemic factors present in whole animals. Expression analysis of cultured skin biopsies from strains of mice with opposing angiogenic response were performed to identify pathways that contribute to differential angiogenic response. Increased expression of negative regulators of angiogenesis in C57Bl/6J mice was associated with lower growth rates.

Heritability of articular cartilage regeneration and its association with ear wound healing in mice

“…In addition, increased angiogenesis, cell proliferation, matrix formation, and fibroblast migration occur in tissue undergoing repair in the healer strains compared to the nonhealer strains. The MRL/MpJ mouse strain has also demonstrated a superior microvasculature response to skin wounds (37). Thus, the healing properties of MRL/MpJ mice, and likely LG/J mice, are a result of multiple pathways and not due to a single cause.…”

Mapping Novel Subcutaneous Angiogenesis Quantitative Trait Loci in [B6×MRL]F2 Mice

“…9 Alternatively, we and others have illustrated divergent outcomes among inbred mouse strains with respect to vessel growth at early stages of wound healing (Fig. 1b), 10,11 suggesting that multiple polymorphisms in mammals contribute to healing at different points in the process.…”

“…To accomplish this goal, we utilized a novel ex vivo culture system that has been described elsewhere. 10 This method focuses on a short window of vessel growth from full-thickness skin biopsies cultured over 7 days. Whereas the process of biopsy isolation is presumed to activate the wound response, our approach should limit this response to tissue intrinsic differences that are present in the skin.…”

“…10 Briefly, euthanized 3-day mice were sanitized and transferred to the Eagle's minimal essential medium containing 1· antibioticantimycotic (Gibco). A 2 cm · 2 cm full-thickness skin segment was removed from the dorsal flank between the scapulae and four 2 mm circular biopsies were isolated with a dermal punch (Miltex).…”

Pattern of inflammatory response to Loxosceles intermedia venom in distinct mouse strains: A key element to understand skin lesions and dermonecrosis by poisoning

“…demonstrated that the venom effect was different at each mouse strains. Data in the literature show functional consequences influenced by the strain of mice, which include: alcoholic tolerance (Bowers et al, 1999), tumor incidence (Donehower et al, 1995), insulin secretion (Andrikopoulos et al, 2005), platelet aggregation, tissue repair (van den Borne et al, 2009) and physiological and pathophysiological angiogenesis (Liu et al, 2010). The occurrence of edema is one of the early events during acute inflammation .…”