title: Cardiovascular risk factors cause premature rarefaction of the collateral circulation and greater ischemic tissue injury.
abstract: BACKGROUND
  Collaterals lessen tissue injury in occlusive disease. However, aging causes progressive decline in their number and smaller diameters in those that remain (collateral rarefaction), beginning at 16 months of age in mice (i.e., middle age), and worse ischemic injury-effects that are accelerated in even 3-month-old eNOS(-/-) mice. These findings have found indirect support in recent human studies.
  
  
  OBJECTIVE
  We sought to determine whether other cardiovascular risk factors (CVRFs) associated with endothelial dysfunction cause collateral rarefaction, investigate possible mechanisms, and test strategies for prevention.
  
  
  RESULTS
  Mice with nine different models of CVRFs of 4-12 months of age were assessed for number and diameter of native collaterals in skeletal muscle and brain and for collateral-dependent perfusion and ischemic injury after arterial occlusion. Hypertension caused collateral rarefaction whose severity increased with duration and level of hypertension, accompanied by greater hindlimb ischemia and cerebral infarct volume. Chronic treatment of wild-type mice with L-N (G)-nitro-arginine methylester caused similar rarefaction and worse ischemic injury which were not prevented by lowering arterial pressure with hydralazine. Metabolic syndrome, hypercholesterolemia, diabetes mellitus, and obesity also caused collateral rarefaction. Neither chronic statin treatment nor exercise training lessened hypertension-induced rarefaction.
  
  
  CONCLUSIONS
  Chronic CVRF presence caused collateral rarefaction and worse ischemic injury, even at relatively young ages. Rarefaction was associated with increased proliferation rate of collateral endothelial cells, effects that may promote accelerated endothelial cell senescence.
authors: Department of Cell Biology and Physiology, 6309 MBRB, University of North Carolina, Chapel Hill, NC, 27599-7545, USA.
authors: Scott M
authors: SM
authors: Moore
authors: Hua
authors: H
authors: Zhang
authors: Nobuyo
authors: N
authors: Maeda
authors: Claire M
authors: CM
authors: Doerschuk
authors: James E
authors: JE
authors: Faber
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases; D049109:Cell Proliferation; D003097:Collateral Circulation / Q000502:physiology*; D005260:Female; D006614:Hindlimb / Q000098:blood supply*; D007150:Immunohistochemistry; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D009389:Neovascularization, Pathologic; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D010805:Physical Conditioning, Animal; D011804:Quinolines / Q000737:chemistry; D012083:Renin / Q000235:genetics; D012307:Risk Factors; D013997:Time Factors
chemical_list: D011804:Quinolines; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D012083:Renin; C108475:pitavastatin; D019331:NG-Nitroarginine Methyl Ester