alpha-Lipoic acid modulates extracellular matrix and angiogenesis gene expression in non-healing wounds treated with hyperbaric oxygen therapy.
alpha-Lipoic acid (LA) has been found previously to accelerate wound repair in patients affected by chronic wounds who underwent hyperbaric oxygen (HBO) therapy. Because proteinases are important in wound repair, we hypothesized that LA may regulate matrix metalloproteinase (MMP) expression in cells that are involved in wound repair. Patients undergoing HBO therapy were double-blind randomized into two groups: the LA group and the placebo group. Gene expression profiles for MMPs and for angiogenesis mediators were evaluated in biopsies collected at the first HBO session, at the seventh HBO session, and after 14 days of HBO treatment. ELISA tests were used to validate microarray expression of selected genes. LA supplementation in combination with HBO therapy downregulated the inflammatory cytokines and the growth factors which, in turn, affect MMPs expression. The disruption of the positive autocrine feedback loops that maintain the chronic wound state promotes progression of the healing process.
Alleva
Renata
R
Department of Anesthesiology, IRCCS Istituti Ortopedici Rizzoli, Bologna, Italy. renalle@libero.it
Tomasetti
Marco
M
Sartini
Davide
D
Emanuelli
Monica
M
Nasole
Emanuele
E
Di Donato
Ferruccio
F
Borghi
Battista
B
Santarelli
Lory
L
Neuzil
Jiri
J
D000368:Aged; D000369:Aged, 80 and over; D019898:Autocrine Communication; D000077214:Becaplermin; D004311:Double-Blind Method; D005109:Extracellular Matrix / Q000201:enzymology*; D025461:Feedback, Physiological; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006931:Hyperbaric Oxygenation; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010919:Placebos; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D008063:Thioctic Acid / Q000378:metabolism / Q000627:therapeutic use; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014945:Wound Healing / Q000235:genetics; D014947:Wounds and Injuries / Q000473:pathology / Q000628:therapy*
D053583:Interleukin-1beta; D015850:Interleukin-6; D010919:Placebos; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D019714:Tissue Inhibitor of Metalloproteinases; D014409:Tumor Necrosis Factor-alpha; D000077214:Becaplermin; D008063:Thioctic Acid; D020782:Matrix Metalloproteinases