Fibrosis, enzymatic and non-enzymatic cross-links in Hypertensive heart disease

Michele M. Ciulla, Roberta Paliotti, Marina Carini, Fabio Magrini, Giancarlo Aldini

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)61-73
Number of pages13
JournalCardiovascular and Hematological Disorders - Drug Targets
Issue number2
Publication statusPublished - Sep 2011


  • Advanced glycation end products (AGEs)
  • Advanced lipoxidation end-products (ALEs)
  • Arterial hypertension
  • Either advanced glycation or lipoxidation endproducts (EAGLEs)
  • Left ventricular remodeling
  • Non-enzymatic cross-linking
  • Reactive oxygen species (ROS)
  • Regresison of myocardial fibrosis

ASJC Scopus subject areas

  • Molecular Medicine
  • Cardiology and Cardiovascular Medicine
  • Hematology
  • Pharmacology


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