Optimizing the host substrate environment for cardiac angiogenesis, arteriogenesis, and myogenesis

ABSTRACT

Introduction: 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.

KEYWORDS:

• Angiogenesis
• arteriogenesis
• cardiovascular disease
• cell therapy
• endothelial dysfunction
• myogenesis
• tissue engineering

Article highlights

• Endothelial dysfunction and decreased nitric oxide (NO) bioavailability in patients impair the potentials of regenerative cell therapy and angiogenic therapy.

• Endothelial dysfunction attenuates the host angiogenic response and reduces the number/function of endogenous circulating progenitor cells.

• The strategies of improving endothelial function would achieve better functional outcomes in patients through promoting host angiogenic capability and becoming more responsive to regenerative therapy.

• Biomaterials can modify the harsh post-myocardial infarction (MI) environment.

• The elucidation of the interaction between biomaterials, the host tissue, and downstream signaling pathways is a key challenge in order to optimize the host substrate environment and develop novel biomaterials.

• This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was supported by the Canadian Institute of Health Research (CIHR); Grant MOP-77536 to M Ruel and EJ Suuronen)