title: Deep tissue injury in development of pressure ulcers: a decrease of inflammasome activation and changes in human skin morphology in response to aging and mechanical load.
abstract: Molecular mechanisms leading to pressure ulcer development are scarce in spite of high mortality of patients. Development of pressure ulcers that is initially observed as deep tissue injury is multifactorial. We postulate that biomechanical forces and inflammasome activation, together with ischemia and aging, may play a role in pressure ulcer development. To test this we used a newly-developed bio-mechanical model in which ischemic young and aged human skin was subjected to a constant physiological compressive stress (load) of 300 kPa (determined by pressure plate analyses of a person in a reclining position) for 0.5-4 hours. Collagen orientation was assessed using polarized light, whereas inflammasome proteins were quantified by immunoblotting. Loaded skin showed marked changes in morphology and NLRP3 inflammasome protein expression. Sub-epidermal separations and altered orientation of collagen fibers were observed in aged skin at earlier time points. Aged skin showed significant decreases in the levels of NLRP3 inflammasome proteins. Loading did not alter NLRP3 inflammasome proteins expression in aged skin, whereas it significantly increased their levels in young skin. We conclude that aging contributes to rapid morphological changes and decrease in inflammasome proteins in response to tissue damage, suggesting that a decline in the innate inflammatory response in elderly skin could contribute to pressure ulcer pathogenesis. Observed morphological changes suggest that tissue damage upon loading may not be entirely preventable. Furthermore, newly developed model described here may be very useful in understanding the mechanisms of deep tissue injury that may lead towards development of pressure ulcers.
authors: Department of Dermatology & Cutaneous Surgery, Wound Healing and Regenerative Medicine Research Program, University of Miami Miller Medical School, Miami, Florida, United States of America.
authors: Olivera
authors: O
authors: Stojadinovic
authors: Julia
authors: J
authors: Minkiewicz
authors: Andrew
authors: A
authors: Sawaya
authors: Jonathan W
authors: JW
authors: Bourne
authors: Peter
authors: P
authors: Torzilli
authors: Juan Pablo
authors: JP
authors: de Rivero Vaccari
authors: W Dalton
authors: WD
authors: Dietrich
authors: Robert W
authors: RW
authors: Keane
authors: Marjana
authors: M
authors: Tomic-Canic
mesh_terms: D000328:Adult; D000375:Aging; D001696:Biomechanical Phenomena; D002352:Carrier Proteins / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D020405:Dermis / Q000293:injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008422:Materials Testing; D008875:Middle Aged; D008954:Models, Biological; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011312:Pressure; D003668:Pressure Ulcer / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D012867:Skin / Q000293:injuries / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D013314:Stress, Mechanical; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D003094:Collagen
references: J Am Acad Dermatol. 1982 Jun;6(6):1014-21
references: 7096663
references: Med Eng Phys. 2001 Apr;23(3):195-200
references: 11410384
references: Int Wound J. 2008 Dec;5(5):615-24
references: 19134062
references: J Surg Res. 2011 Dec;171(2):700-8
references: 22005503
references: Am J Pathol. 2006 Aug;169(2):482-90
references: 16877350
references: Case Manager. 2002 Jul-Aug;13(4):61-4; quiz 65
references: 12131910
references: Cell Mol Life Sci. 2012 Sep;69(18):2999-3013
references: 22446749
references: Wound Repair Regen. 2002 Jan-Feb;10(1):26-37
references: 11983004
references: Arthritis Rheum. 2009 Dec;60(12):3642-50
references: 19950258
references: Wound Repair Regen. 2007 Jan-Feb;15(1):71-9
references: 17244322
references: Wound Repair Regen. 2011 Nov;19(6):734-44
references: 22092844
references: J Invest Dermatol. 2001 May;116(5):633-40
references: 11348449
references: J Cereb Blood Flow Metab. 2009 Jul;29(7):1251-61
references: 19401709
references: Curr Biol. 2007 Jul 3;17(13):1140-5
references: 17600714
references: Photodermatol Photoimmunol Photomed. 1994 Apr;10(2):47-52
references: 8043384
references: Am J Clin Nutr. 2006 Feb;83(2):447S-455S
references: 16470011
references: Wound Repair Regen. 2008 May-Jun;16(3):460-5
references: 18471264
references: Plast Reconstr Surg. 2011 Jan;127 Suppl 1:105S-115S
references: 21200280
references: Plast Reconstr Surg. 2011 Dec;128(6):721e-727e
references: 21841528
references: J Histochem Cytochem. 2002 Nov;50(11):1469-74
references: 12417612
references: J Biomech. 1997 Jan;30(1):1-9
references: 8970918
references: J Dermatol Sci. 1998 Jul;17(3):167-81
references: 9697045
references: Immunol Lett. 2012 Sep;147(1-2):29-33
references: 22698681
references: J Invest Dermatol. 2011 Nov;131(11):2316-22
references: 21833012
references: J Hosp Infect. 2013 Apr;83(4):314-20
references: 23313027
references: Ann Biomed Eng. 2009 May;37(5):1007-18
references: 19234790
references: Vet Dermatol. 2009 Oct;20(5-6):515-32
references: 20178490
references: Dermatol Clin. 1986 Jul;4(3):433-46
references: 3521988
references: Cell Rep. 2012 Jan 26;1(1):56-68
references: 22832107
references: Foot Ankle Int. 2009 May;30(5):405-9
references: 19439139
references: Arch Phys Med Rehabil. 1998 Mar;79(3):265-72
references: 9523777
references: Arch Surg. 2000 Oct;135(10):1148-53
references: 11030870
references: J Prev Med Hyg. 2012 Mar;53(1):30-6
references: 22803317
references: PLoS One. 2010 Jul 23;5(7):e11765
references: 20668705
references: J Invest Dermatol. 2011 Mar;131(3):670-6
references: 21191419
references: Cartilage. 2011 Oct 1;2(4):364-373
references: 22039566
references: Decubitus. 1990 Nov;3(4):20-4
references: 2242233
references: JAMA. 2003 Jan 8;289(2):223-6
references: 12517234
references: Mol Cell Biochem. 1999 Apr;194(1-2):99-108
references: 10391129
references: Cytokine Growth Factor Rev. 1997 Dec;8(4):253-65
references: 9620641
references: Nurs Econ. 1999 Sep-Oct;17(5):263-71
references: 10711175
references: Surg Technol Int. 2003;11:161-7
references: 12931298
references: Swiss Med Wkly. 2012 May 31;142:w13590
references: 22653747
references: Technol Health Care. 2007;15(3):195-202
references: 17473399
references: Eur J Cell Biol. 2010 Sep;89(9):638-44
references: 20605059
references: Acta Derm Venereol. 2009;89(5):459-65
references: 19734969
references: Plast Reconstr Surg. 1998 Sep;102(4):1023-7; discussion 1028-9
references: 9734419
references: Arthritis Rheum. 2009 Dec;60(12):3651-62
references: 19950280
references: Skin Res Technol. 2006 Aug;12(3):145-54
references: 16827688
references: J Biol Chem. 2010 Jan 15;285(3):1980-8
references: 19903814
references: Arch Phys Med Rehabil. 1959 Feb;40(2):62-9
references: 13618101
references: Cell Death Differ. 2007 Jan;14(1):10-22
references: 16977329
references: Exp Dermatol. 2011 Dec;20(12):1027-9
references: 22092578
references: J Biol Chem. 2011 Mar 25;286(12):10265-75
references: 21239489
references: J Tissue Viability. 2010 May;19(2):67-76
references: 20006504
references: Ostomy Wound Manage. 2007 Oct;53(10):40-9
references: 17978414
references: J Immunol. 2008 Jun 1;180(11):7147-57
references: 18490713
references: Int J Dermatol. 2005 Oct;44(10):805-10
references: 16207179
references: Sci Transl Med. 2011 May 11;3(82):82ra38
references: 21562230
references: Plast Reconstr Surg. 1980 Nov;66(5):728-33
references: 7001518
references: Dermatology. 2011;223(3):266-84
references: 22116308
references: J Cereb Blood Flow Metab. 2009 Mar;29(3):534-44
references: 19066616
references: Wound Repair Regen. 2007 Mar-Apr;15(2):203-12
references: 17352752
references: J Immunol. 2012 Mar 15;188(6):2866-75
references: 22331066
references: Exp Dermatol. 2007 Jul;16(7):567-73
references: 17576236
references: J Neurosci. 2008 Mar 26;28(13):3404-14
references: 18367607
references: J Immunol. 2012 Feb 15;188(4):1992-2000
references: 22246630
references: Mol Med. 2010 Mar;16(3-4):92-101
references: 20069132
references: J Gerontol A Biol Sci Med Sci. 2006 Jul;61(7):749-54
references: 16870639
references: Immunity. 2012 Jul 27;37(1):85-95
references: 22819042
references: J Spinal Cord Med. 2007;30(2):107-16
references: 17591222
references: Adv Skin Wound Care. 2005 Jan-Feb;18(1):35-42
references: 15714036