Page 16 - Read Online
P. 16

proliferation, migration,  capillary tube  formation and   Galiano et al.  found that topical VEGF accelerates wound
                                                                         [78]
          deposition of ECM. [60,61]                          healing in a diabetic mouse model.
          The angiopoietins are members of the VEGF family, which   Weinheimer‑Haus  et  al.  found that low intensity
                                                                                   [79]
          is largely specific for vascular endothelium. They include a   vibration (LIV) applied vertically at 45 Hz with peak
          naturally occurring agonist, Ang‑1, and antagonist, Ang‑2,   acceleration of 0.4 g for 30 min a day for 5 days a week
          both of which act by means of the Tie‑2 receptor. Two   starting  on  the  day  of  injury  in  diabetic  mice  increases
          new angiopoietins,  Ang‑3 in mice and Ang‑4 in humans,   expression of pro‑healing growth factors and chemokines
          have been identified, but their function in angiogenesis is   (insulin‑like growth factor‑1, VEGF and monocyte
          unknown. [62]                                       chemotactic protein‑1) in wound environment. Though
                                                              there was no evidence of a change in the phenotype
          Mast cell tryptase, stored in granules of activated mast cells,
          is an additional angiogenesis factor that directly degrades   of CD11b+  macrophages, however, LIV resulted in
          the  ECM  components  or  release  matrix‑bound  growth   trend toward a less inflammatory phenotype in the
          factors by its proteolytic activity, [63,64]  and acts indirectly   CD11b2 cells which comprised of fibroblasts, endothelial
          by activating latent matrix metalloproteases. The addition   cells and/or keratinocytes. These findings indicate that
          of tryptase to microvascular endothelial cells cultured on   LIV  may  exert  beneficial  effects  on  wound  healing  by
          a basement membrane matrix (matrigel) caused a marked   enhancing angiogenesis and granulation tissue formation,
          increase in capillary growth. Furthermore, tryptase  can   and these changes are associated with an increase in
                                                                                        [79]
          induce endothelial cell proliferation in a dose‑dependent   pro‑angiogenic growth factors.
          manner, whereas specific tryptase inhibitors  suppress  the   Venous insufficiency ulcers
          capillary growth. [65]                              Venous  insufficiency  ulcers or venous  stasis  ulcers result
                                                              from incompetent valves in lower extremity veins, leading
          IMPAIRED ANGIOGENESIS IN CHRONIC                    to venous stasis and  hypertension that makes the skin
          WOUNDS                                              susceptible to ulceration. Pathological findings associated
                                                              with venous stasis  ulcers include microangiopathy,
          Angiogenesis  is impaired in all chronic wounds leading   fibrin  “cuffing” and trapping of leukocytes within  the
          to further tissue damage results from chronic hypoxia   microvasculature. [80,81]
          and impaired micronutrient delivery. Specific defects have   Chronic venous stasis ulcer patients have elevated levels
          been  identified  in diabetic ulcers, venous insufficiency   of VEGF in their  circulation.  This may  explain the
                                                                                        [82]
          ulcers and ischemic ulcers.                         vascular permeability and increased transudation of serum
          Diabetic ulcers                                     fluid in their wounds. Biopsies of these ulcers  reveal
          Patients with diabetes show abnormal angiogenesis in   microvessels that are surrounded by fibrin cuffs composed
          various organs. Vasculopathies associated with diabetes   of fibrin and plasma proteins, such as  α‑macroglobulin,
          include abnormal blood vessel formation  (e.g.  retinopathy,   thought to compromise gas exchange. [83‑85]  Clinical studies
          nephropathy) and accelerated atherosclerosis leading   have shown that transcutaneous oxygen  tension  may  be
          to coronary artery disease, peripheral vascular disease,   up to 85% lower in venous stasis ulcers compared with
                                                                               [86]
          and cerebrovascular disease.  However, in diabetics,   normal skin regions.  VEGF expression is up‑regulated by
                                   [65]
          angiogenesis is decreased  resulting in poor formation   hypoxia,  which further exacerbates vascular permeability,
                                [66]
          of new blood vessels and thus decreased entry of    formation of pericapillary fibrin cuffs and compromised
          inflammatory cells and their growth factors. Growth factors   gas exchange, which ultimately reduces growth factor
          such  as  FGF‑2  and  PDGF,  essential  for  wound  healing   availability  in  the  wound. [87,88]   VEGF  promotes  the
          have  been found to be reduced  in  experimental  diabetic   formation  tortuous,  aberrant  glomeruloid‑like  vascular
                                                                                                   [89]
          wounds  models. [67‑70]   Furthermore,  in  rat  models,  topical   structures  found in  granulation  tissue.   Laboratory
          administration of high glucose to wounds was shown to   animals  treated  with  VEGF  form  these  glomeruloid
                                         [71]
          inhibit the normal angiogenic process,  suggesting a direct   vascular structures  within  3  days  and are  characterized
                                                                              [90]
          role for high glucose levels in diminished angiogenesis.  by poor perfusion.  In venous ulcers, the persistence of
                                                              glomeruloid vessels may interfere with oxygen  delivery
          Vascular endothelial growth factor plays an important   and  delay healing. In chronic venous stasis ulcers,
          role in vascular growth and has been shown to be    high  levels of proteases  such as  neutrophil elastase,
          deficient in diabetic wounds in experimental and clinical   MMPs  and urokinase‑type  plasminogen  activator are
          models.  Studies have shown that modulation of      present.  Concomitantly,  there  are decreased levels
                [72]
                                                                     [91]
          oxidative damage  or inhibition of the receptors for   of protease  inhibitors,  such  as  plasminogen  activator
                         [73]
          advanced glycation end products  improve wound healing   inhibitor‑2. Excessive protease activity may degrade the
                                     [74]
          and were associated with the up‑regulation of endogenous   growth factors and destroy granulation tissue.
          VEGF. Moreover, VEGF administration improves wound
          healing in nondiabetic ischemic wounds  and blocking   Ischemic ulcers
                                             [75]
          VEGF with neutralizing antibodies impedes tissue repair.    Peripheral arterial  disease  (PAD) may  result  in  severe
                                                         [76]
          These studies support the notion that VEGF is critical for   ischemia.  Reduce tissue  perfusion due to ischemia
                                                                      [92]
          repair  in  impaired  healing states and that  the  addition   results in progressive tissue hypoxia, ischemia,  necrosis
          of VEGF could have a potential clinical use.  In fact,   and skin  breakdown. In  theory,  tissue  hypoxia  should
                                                 [77]
           246                                                           Plast Aesthet Res || Vol 2 || Issue 5 || Sep 15, 2015
   11   12   13   14   15   16   17   18   19   20   21