title: Altered angiogenic balance in keloids: a key to therapeutic intervention.
abstract: Keloids are manifestations of abnormal wound repair with unresolved clinical complications. An effective therapeutic regimen has not been established for keloids, and current strategies are plagued by problems such as recurrence and side effects. Keloids, being a human-specific dermal fibroproliferative disorder are characterized by an excessive accumulation of extracellular matrix (ECM), thickened basement membrane, unregulated expression of matrix metalloproteases, growth factors, and cytokines. The internal milieu in a keloid bears a strong resemblance to a tumor with both exhibiting striking similarities with respect to tissue environment and unregulated vasculature. Abnormal angiogenesis manifested by an imbalance between proangiogenic and antiangiogenic factors has been recognized as a "common denominator" underlying many pathological conditions. However, such an imbalance has not been investigated in keloids. In this study, the angiogenic imbalance in keloids was explored with reference to circulating and tissue level expression of vascular endothelial growth factor (VEGF) and endostatin/collagen XVIII. It was observed that VEGF levels were upregulated and endostatin levels were downregulated in keloid patients in comparison to normal controls in both sera and tissue. Hence, antiangiogenic therapeutics based on endostatin in combination with current curative strategies as in tumors would present a scope for the effective management of keloids.
authors.affiliation: Biomaterials Division, Central Leather Research Institute, TICEL Biopark, CSIR Road, Taramani, Chennai, Tamil Nadu, India.
authors.forename: Nirupa Shyam
authors.initials: NS
authors.lastname: Mogili
authors.forename: Venkat Raghavan
authors.initials: VR
authors.lastname: Krishnaswamy
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Jayaraman
authors.forename: Rama
authors.initials: R
authors.lastname: Rajaram
authors.forename: Alamelu
authors.initials: A
authors.lastname: Venkatraman
authors.forename: Purna Sai
authors.initials: PS
authors.lastname: Korrapati
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D016022:Case-Control Studies; D002648:Child; D043170:Collagen Type XVIII / Q000378:metabolism; D003131:Combined Modality Therapy; D015536:Down-Regulation; D043169:Endostatins / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D007627:Keloid / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D043170:Collagen Type XVIII; D043169:Endostatins; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A