**Vascular Smooth Muscle as a Therapeutic Target in Disease Pathology**

Andrew W. Holt and David A. Tulis

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/60878

#### **Abstract**

Our circulatory system is composed of numerous elements that are responsible for transport of blood and delivery of essential nutrients and gases to vital downstream tissues. Among these components that make up our circulation is vascular smooth muscle (VSM), the primary muscular and contractile element of blood vessels and regulator of many blood vessel functions. This is of particular importance as cardio‐ vascular disease (CVD), the number one killer of individuals in America and worldwide, is primarily vascular in origin. Logically, identifying and characterizing feasible targets that could control CVD are highly appealing and much desired. With this in mind and given its centrality in control of vascular physiology, VSM has gained wide attention as a plausible target to combat elements of CVD. This book chapter focuses on VSM as a potential therapeutic target against CVD and will provide overview of vascular anatomy and physiology and brief discussions about the pivotal roles of VSM in CVD pathology, the influence of abnormal blood flow mechanics and hemodynamics in CVD, neural control of VSM and the vasculature, and possible novel cellular and molecular signaling targets that could be used to control and/or minimize CVD. This chapter hopes to serve as a valuable resource for basic and applied scientists as well as clinicians interested in understanding the crucial roles that VSM plays in vessel physiology and pathology.

**Keywords:** Cardiovascular disease, cell signaling, cyclic nucleotides, hemodynam‐ ics, kinases, shear stress, vascular smooth muscle

© 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

## **1. Introduction**

Our circulatory system is comprised of a vast network of cellular elements and organs that includes the heart, lungs, and vasculature composed of arteries, veins, and lymphatics. These integrated factors serve essential roles in controlling flow of blood and lymph and in the transport and delivery of essential nutrients, nutritive and vasoactive factors, and hormones and gases. Vascular smooth muscle (VSM), the primary functional constituent of blood vessels, serves critical regulatory roles of vessel relaxation and contraction to ensure adequate tissue blood flow and to maintain proper localized arterial blood pressures and perfusion of downstream tissues. These processes are elemental for normal vascular eutrophy and homeo‐ stasis and overall body health. Abnormalities in VSM anatomy and physiology, however, can contribute to a myriad of primary and secondary vessel pathologies. Moreover, adult blood vessels are normally contractile, quiescent, and static. However, under inimical conditions like those associated with cardiovascular disease (CVD), VSM cells undergo phenotypic alterations and revert to a growth-promoting, synthetic nature. In turn, this abnormal growth significantly contributes to the emerging cardiovascular disorder. These complications alone present significant health risks but also serve as confounding risk factors for associated cardiovascular complications including hypertension, hypercholesterolemia, diabetes, and metabolic syn‐ drome. In fact, recent statements by the American Heart Association [1] and the World Health Organization [2] point to dysfunctional VSM as a primary underpinning behind CVD. Logically, therapeutically targeting VSM for clinical interventions aimed at controlling and hopefully eradicating CVD is highly significant and essential.

The term "cardiovascular disease" defines a wide range of disorders, diseases, and conditions that deleteriously affect the heart and blood vessels. If the heart is the primary organ affected then this can include heart failure, various myopathies, arrhythmias and/or conduction delays, valve complications, myocarditis and/or pericarditis. If the disorder is vascular in origin, then problems could consist of occlusive plaque formation and atherosclerosis, arteriosclerosis, coronary and/or peripheral artery disease (PAD), aneurysm formation, and/or restenosis and remodeling. There are numerous forms and manifestations of CVD as well as broad prognoses based on form and severity of the disorder. Abnormal biology of the vessel wall constitutes a major element in the pathogenesis of most forms of CVD [1], and therefore the vessel wall and particularly VSM makes a prime target for further discovery and potential therapeutic utility against CVD.

The overall goal of this chapter is to present some of the more recent and novel theories surrounding the primary vessel wall constituent, VSM, its importance in CVD, and its promise as a therapeutic target. Discussion will include succinct overviews of normal vascular elements and physiology with a focus on VSM, some common forms of CVD and their pathologies, the role of VSM dysfunction in CVD etiology, the influence of flow alterations and hemodynamic forces in vessel physiology and pathology, neural control of VSM and the vascular network, unique molecular and cellular signaling pathways that may offer innovative and precise targets for therapy in VSM, current therapeutic paradigms, and treatment strategies used to combat VSM pathobiology ranging from homeopathic lifestyle modifications to pharmaco‐ therapies to interventional vascular approaches. This chapter concludes with an overview of the therapeutic potential of VSM and its promise in the cardiovascular sciences. In all, this chapter promises to offer a valuable resource for basic, applied, and clinical scientists by providing a synopsis of the importance of VSM in normal vessel biology and vascular pathology and its utility as therapeutic target to combat CVD.
