title: Optimizing the host substrate environment for cardiac angiogenesis, arteriogenesis, and myogenesis.
abstract: The diseased host milieu, such as endothelial dysfunction (ED), decreased NO bioavailability, and ischemic/inflammatory post-MI environment, hamper the clinical success of existing cardiac regenerative therapies. Area covered: In this article, current strategies including pharmacological and nonpharmacological approaches for improving the diseased host milieu are reviewed. Specifically, the authors provide focus on: i) the mechanism of ED in patients with cardiovascular diseases, ii) the current results of ED improving strategies in pre-clinical and clinical studies, and iii) the use of biomaterials as a novel modulator in damaged post-MI environment. Expert opinion: Adjunct therapies which improve host endothelial function have demonstrated promising outcomes, potentially overcoming disappointing results of cell therapy in human studies. In the future, elucidation of the interactions between the host tissue and therapeutic agents, as well as downstream signaling pathways, will be the next challenges in enhancing regenerative therapy. More careful investigations are also required to establish these agents' safety and efficacy for wide usage in humans.
authors.affiliation: a Divisions of Cardiac Surgery , University of Ottawa Heart Institute , Ottawa , ON , Canada.
authors.forename: Kay
authors.initials: K
authors.lastname: Maeda
authors.affiliation: a Divisions of Cardiac Surgery , University of Ottawa Heart Institute , Ottawa , ON , Canada.
authors.forename: Emilio I
authors.initials: EI
authors.lastname: Alarcon
authors.affiliation: a Divisions of Cardiac Surgery , University of Ottawa Heart Institute , Ottawa , ON , Canada.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Suuronen
authors.affiliation: a Divisions of Cardiac Surgery , University of Ottawa Heart Institute , Ottawa , ON , Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Ruel
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D001672:Biocompatible Materials / Q000494:pharmacology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006801:Humans; D024510:Muscle Development / Q000187:drug effects / Q000502:physiology*; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D014652:Vascular Diseases / Q000175:diagnosis / Q000188:drug therapy
chemical_list: D001672:Biocompatible Materials
keywords: Angiogenesis; arteriogenesis; cardiovascular disease; cell therapy; endothelial dysfunction; myogenesis; tissue engineering