Document Detail


Fibrosis, enzymatic and non-enzymatic cross-links in hypertensive heart disease.
MedLine Citation:
PMID:  22044034     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Myocardial fibrosis is commonly observed in left ventricular (LV) hypertrophied heart during Arterial Hypertension. This pathological change coupled with vascular stiffening with aging and diabetes may reduce the cardiovascular system elasticity contributing to the functional impairment. Both the LV adaptive response to the increasing blood pressure and the oxidative damage contribute to myocardial fibrosis; in particular, reactive oxygen species (ROS) induce the formation of reactive electrophilic carbonyl species by reacting with lipids and sugars which in turn react with proteins forming irreversible adducts (AGEs, ALEs and EAGLEs) and cross-links. The vascular wall matrix then becomes less distensible, as the formation of the adducts induces greater capacity in collagen to resist normal turnover. Therefore, monitoring cardiac fibrosis and markers of collagen synthesis, degradation and non-enzymatic cross-linking and the use of drugs that revert collagen accumulation and/or prevent/repair non-enzymatic cross-linking might represent a novel opportunity to alter the natural history of hypertensive heart disease. Recent evidences have suggested to target the excess of collagen cross-links; initial evidence seems to show that fibrosis is not affected to the same degree by all anti-hypertensive agents. ACEI and ARBs appear particularly effective. Finally, agents acting as cross-link breakers on AGEs or preventing AGEs formation or affecting the TTG activity are emerging.
Authors:
M M Ciulla; R Paliotti; M Carini; G Aldini
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-26
Journal Detail:
Title:  Cardiovascular & hematological disorders drug targets     Volume:  -     ISSN:  1871-529X     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-11-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101269160     Medline TA:  Cardiovasc Hematol Disord Drug Targets     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Università di Milano, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Via F. Sforza 35 - 20122 Milano, Italy. michele.ciulla@unimi.it.
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