Vascular smooth muscle phenotypic diversity and function

Abstract

The control of force production in vascular smooth muscle is critical to the normal regulation of blood flow and pressure, and altered regulation is common to diseases such as hypertension, heart failure, and ischemia. A great deal has been learned about imbalances in vasoconstrictor and vasodilator signals, e.g., angiotensin, endothelin, norepinephrine, and nitric oxide, that regulate vascular tone in normal and disease contexts. In contrast there has been limited study of how the phenotypic state of the vascular smooth muscle cell may influence the contractile response to these signaling pathways dependent upon the developmental, tissue-specific (vascular bed) or disease context. Smooth, skeletal, and cardiac muscle lineages are traditionally classified into fast or slow sublineages based on rates of contraction and relaxation, recognizing that this simple dichotomy vastly underrepresents muscle phenotypic diversity. A great deal has been learned about developmental specification of the striated muscle sublineages and their phenotypic interconversions in the mature animal under the control of mechanical load, neural input, and hormones. In contrast there has been relatively limited study of smooth muscle contractile phenotypic diversity. This is surprising given the number of diseases in which smooth muscle contractile dysfunction plays a key role. This review focuses on smooth muscle contractile phenotypic diversity in the vascular system, how it is generated, and how it may determine vascular function in developmental and disease contexts.

Calcium Cycling in Synthetic and Contractile Phasic or Tonic Vascular Smooth Muscle Cells

“…Phasic vascular smooth muscle refers to blood vessels displaying rhythmic contractile activity whereas tonic vascular smooth muscle refers to blood vessels displaying continuous contractions [61]. Phasic contraction is the characteristic of small resistance arteries (SRA, 20-50 µm diameters) which predominantly regulates vascular functions such as pressure and flow.…”

“…For instance, phasic contractions displayed by small arteries of the heart and lung, muscular femoral artery, small mesenteric arteries and renal afferent arteriole result from the VSMC expression of the fast isoform of smooth muscle myosin heavy chain (MHC) which determines the velocity of shortening during vasomotion (rev. [61]). Of note, lent isoform of smooth muscle myosin, so called "non muscular myosin, (NM-B)" is expressed in all types of VSMCs including synthetic/proliferating VSMC; it plays a significant role in force maintenance during tonic contraction [58,61].…”

Vascular Smooth Muscle Cells in the Branching of Renal Arteries

“…It is important to bear in mind that the pressure (stress / strain) and fl ow (shear) can regulate the function of blood [9], differentiation, proliferation and migration of vascular myocytes [9,10].…”

“…Thus, these data confi rm the information [10,21] about the heterogeneity of the SM populations. Isolated phenotype small phase (fast) SM, capable of passing through hypertrophic growth and tonic (slow) vascular SM undergoing hyperplasia [9]. Load changes can cause phenotypic modulation of myocyte proliferation and SM [9,10].…”

“…Isolated phenotype small phase (fast) SM, capable of passing through hypertrophic growth and tonic (slow) vascular SM undergoing hyperplasia [9]. Load changes can cause phenotypic modulation of myocyte proliferation and SM [9,10]. Thus, hemodynamic conditions can be a factor affecting the properties SM vascular wall.…”