ABSTRACT
The incidence of heart failure has increased over the last decades, primarily because of the expansion of the “modern” lifestyle to developing countries and the lengthening of life expectancy in the West. Despite advancements in the management of heart failure, it still remains a leading cause of death worldwide. Excluding life-style changes, this situation can only be reversed through the development of novel therapeutic strategies. For this to occur, we need to improve our understanding of the mechanisms leading to heart failure and find new drugs. The unearthing of the micro-RNA-mediated gene expression network, its involvement in patho-genesis, and the ability to target/use microRNAs for therapeutic ends has produced much excitement in the scientific community
in this regard. However, before miRNA-based therapeutics can become a reality, we need a suitable cardiac-specific drug delivery system. In this chapter, we give brief overviews of heart failure and microRNAs, and discuss the development of an innovative therapeutic strategy based on novel biocompatible and bioresorb-able nanoparticles for carrying miRNA-based therapeutics to the heart. 10.1 IntroductionCardiovascular diseases (CVDs) are a heterogeneous collection of pathologies affecting the heart and circulatory system. Over the last 30 years, significant improvements have been made in the way CVDs are diagnosed and treated surgically [1]. Despite this-and a better awareness of the impact of diet and life-style-mortality and morbidity from CVD remains unacceptably high: In fact, CVD remains a leading reason for hospitalization and the largest cause of mortality, claiming more lives than cancer in the Western world.For many types of CVD, therapy is palliative, slowing the progression of disease: The only real cure remains heart transplantation because there are no regenerative therapies available to overcome the cardiomyocyte loss that is part of the common final stage of many CVDs, known as heart failure [2]. Therefore, novel strategies are needed if we are to make any new advancement in the treatment of CVD. To this end, a better understanding of cardiovascular pathophysiology is paramount, as are parallel advances in the development of new classes of pharmaceuticals and innovative and organ-specific modes of drug delivery. The relatively recent discovery of non-protein coding RNAs (ncRNAs) as modulators of gene expression has opened up these areas of research. In fact, as we will see in this chapter, an abundant class of ncRNAs intimately linked to cardiac development and physiology may be central to the pathological modifications underlying CVDs, and, thus, may be taken advantage of therapeutically. In addition, cutting-edge nanoparticle-mediated drug delivery approaches may be instrumental for this innovative therapeutic strategy to come about.
