About this Research Topic
Ischemic heart disease is still the leading cause of death around the globe despite the evolution of our knowledge in biology and the advancement in patient care. Occlusion of coronary arteries induces ischemia followed by rapid upregulation of pro-inflammatory cytokines, increased oxidative stress and MMP2 activity, leading to an enhanced apoptosis of cardiac myocytes. Extended ischemia, coupled with reperfusion, lead to massive death of cardiomyocytes and inflammatory infiltration within the infarcted area, resulting in ventricular dysfunction, acute failure, with potentially fatal consequences. Over time, ventricular remodeling takes place, including formation of non-contractile fibrous scar tissue, thinning of the myocardial wall, revascularization in the periinfarct area, followed by progressive compensatory and later maladaptive hypertrophy and dilation of the ventricle, which no longer compensate for the loss of cardiac tissue, leading ultimately to congestive heart failure and death. The current therapy is primarily symptomatic, therefore novel, mechanistic-based therapeutic approaches are needed.
Current therapies of cardiac ischemia, myocardial infarction (MI) and heart failure, aiming to preserve and improve ventricular function and clinical outcomes, include pharmacological interventions, surgical procedures, or mechanical left ventricular assist devices. Although mitigation of chronic ischemia and early reperfusion of the occluded artery, by means of coronary angioplasty and/or stent placement, can decrease infarct size, the loss of cardiac myocytes inevitably begins rapidly following ischemia, inducing permanent damage to the left ventricle. Several novel regenerative strategies addressing ischemic myocardium have demonstrated considerable experimental and clinical benefits.
Targeted delivery of small molecule drugs and advanced therapeutic modalities (cell-, growth factor- or RNA therapeutics) represents a novel and disruptive therapeutic modality with high potential for improving the ventricular function and patients’ outcomes, but their clinical translation is hampered by challenges related to tissue specificity, safety/tolerability, the complexity of drug development and regulatory pathway, as well as manufacturing.
Novel targeting strategies for therapeutic agents are therefore urgently needed, including e.g., targeted delivery of small molecule drugs, biologics, RNA therapeutics, cells, utilizing conjugations or drug-releasing biomaterials carriers for local support, as well as delivery of therapeutics loaded into biocompatible nanoparticles.
This research topic invites articles specifically addressing targeted delivery strategies that reduce ischemic burden, infarct expansion, limit infarct size, enhance re-vascularization of infarcted myocardium, reduces adverse cardiac remodeling, thereby prevent, and improve myocardial function. Manuscripts are sought that describe the advanced delivery approaches in this area, with focus on cardioprotective or regenerative therapeutics that increase treatment efficacy, reduce side effects and improves pharmacology and toxicology.
Submissions are welcome for the following article types: original research, review, mini-reviews, research protocol/method, opinion, and hypothesis.
Keywords: Cardiomyocyte-targeted Drug Delivery, Targeting of Biologics to Ischemia/reperfusion, Nanoparticle-Based Drug Delivery, Drug Conjugates, Targeted RNA Therapeutics, Magnetic Targeting, Targeted Regenerative Approaches
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