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The Journal of Cardiovascular Surgery 1999 April;40(2):257-60


lingua: Inglese

Matrix metalloproteinases. Their role in degenerative chronic diseases of abdominal aorta

Palombo D., Maione M. **, Cifiello B. I. **, Udini M., Maggio D., Lupo M. *

From the Division of Vascular Surgery Department of Cardiac and Vascular Diseases * Service of Anesthesiology and Resuscitation Mauriziano ”Umberto I“ Hospital, Turin, Italy ** Operative Unit of Vascular Surgery Regional Hospital of Valle d’Aosta, Aosta, Italy


Back­ground. The ­main ­chronic degen­er­a­tive dis­eases of the abdom­inal ­aorta, ­namely aneu­rys­matic and ­steno-obstruc­tive pathol­o­gies, ­have a ­common denom­i­nator: ath­ero­scler­osis. ­Both pathol­o­gies are char­ac­ter­ised by the destruc­tion of the struc­tural integ­rity of the extra­cel­lular pro­tein ­matrix (ME). A ­number of ­studies ­have ­shown the pres­ence and involve­ment of a ­group of ­enzymes ­with pro­te­o­lytic ­activity ­towards one or ­more ME com­po­nents, the ­matrix met­al­lop­ro­tei­nases (­MMPs), in the path­o­gen­esis of aneu­rysms of the abdom­inal ­aorta. ­Other ­authors ­have under­lined the ­role of ­MMPs in the pro­life­ra­tion and migra­tion pro­cess of ­smooth ­muscle ­cells ­into the ­intima in the path­o­gen­esis of ather­o­masic ­plaque. The aim of ­this ­study was to eval­uate the pos­sible ­role of ­these ­enzymes in the path­o­gen­esis of ­chronic degen­er­a­tive dis­eases of the ­aorta.
­Methods. Frag­ments of ­aortic ­wall ­were ­removed ­from ­patients under­going elec­tive ­aortic sur­gery for aneu­rysms (14 ­patients) or ­aortic ­steno-obstruc­tion (4 ­patients). The sam­ples ­obtained ­were ­treated appro­pri­ately and ­then sub­ject to immu­no­his­to­chem­ical anal­ysis. The prep­ar­a­tions ­were incu­bated ­with spe­cific ­anti-MMP anti­bodies and ­were ­also incu­bated ­with sub­strate and chro­mogen, ­forming a pig­mented pre­cip­i­tate on the ­site of the ­antigen, ­before ­being ­observed ­using an ­optic micro­scopic at an enlarge­ment of 250×. ­Nuclear pos­i­tivity ­linked to the pres­ence of the ­antigen tes­ti­fied the ­validity of ­staining. ­Lastly, the MMP ­INDEX, or in ­other ­words the ­number of pos­i­tive ­cells out of 100, was ­stained in the adven­titia and in the ­tunica ­media in ­each prep­ar­a­tion.
­Results. ­MMPs ­were ­divided ­into ­three ­main ­groups: inter­sti­tial col­lag­e­nase (MMP1) ­which ­degrade ­type I and III ­native col­lagen; gel­a­ti­nases (MMP9, MMP2) ­which act on ­elastin and ­type IV col­lagen; stro­mel­y­sins (MMP3) ­with spe­cific pro­te­o­lytic ­action ­towards pro­te­og­ly­cans, fibro­nectin and lam­i­nine. In our expe­ri­ence, ­those prep­ar­a­tions ­obtained ­from ­aorta ­affected by ­steno-obstruc­tive pathol­o­gies (4 ­patients) ­revealed the pres­ence of ­MMPs ­with a pref­e­ren­tial local­isa­tion on the ­intimal ­side of the ­tunica ­media. In par­tic­ular, the ­increased ­activity of gel­a­ti­nases MMP9 in ath­e­ros­cle­rotic ­aorta ­might be respon­sible for ­destroying the ­internal ­elastic ­lamina and fos­tering the pro­life­ra­tion and migra­tion of ­smooth ­muscle ­cells and the for­ma­tion of ather­o­masic ­plaque. On the ­other ­hand, prep­ar­a­tions ­obtained ­from aneu­rys­matic ­aorta (14 ­patients) ­showed an oppo­site sit­u­a­tion ­with a pref­e­ren­tial local­isa­tion ­within the adven­titia and on the adven­ti­tial ­side of the ­media. ­Above all, the ­loss of ­elastin rep­re­sents an essen­tial ­stage in the for­ma­tion of ­aortic aneu­rysms.
Con­clu­sions. ­This ­study con­cords ­with ­numerous ­authors who ­have dem­on­strated the involve­ment of pro­tei­nase ­MMPs in the devel­op­ment of ­aortic aneu­rysms and ­their pos­sible ­role in the path­o­gen­esis of ather­o­masic ­plaque.
The dif­ferent ­origin of ­these ­enzymes (inflam­ma­tory ­cells and mac­ro­phages or endo­the­lial ­cells) may be the ­result of dif­ferent pathog­e­netic mech­a­nisms. ­Although ­they ­present dif­ferent pathog­e­netic fea­tures, ­aortic aneu­rysms and ­steno-obstruc­tions ­have a ­common denom­i­nator in ath­ero­scler­osis. The mech­a­nisms respon­sible for ­their evo­lu­tion ­towards one or ­other ­form are not ­known. The dif­ferent expres­sion of ­MMPs in the con­text of the ­aortic ­wall rep­re­sents a ­field for ­future ­research.

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