Cellular organisation in the heart

↳ This is a section part of Moment: Cellular Communications In The Heart

Add this Moment to your Passport

Learn from this moment and keep it forever.
FREE
Add To Passport

Preview

Summary

Cellular organisation in the heart

Cardiac myocytes

The human heart contains an estimated 2–3 billion CM cells, which constitute about 75 % of the total volume of the myocardium, although only about one third of the total cell number.6,7 The major function of the CM is to carry out the cardiac contraction-relaxation cycle. Electrically, CM depolarise in response to signals from the sinoatrial node. Calcium is responsible for translation of the signal into muscular contraction, with calsequestrin in the sarcoplasmic reticulum being the major calcium-binding and storage protein. Mutation of this receptor can lead to a pathologic state of the myocardium, in which delayed after-depolarisation becomes prevalent.4,8

CM can act via chemical signalling by secreting various growth factors and cytokines.9,10,11,12 Moreover, they have been shown to exhibit a mechano-electrical feedback, in which mechanical force influences the electrical potential of the myocyte membrane.13

Cardiac fibroblasts

The majority of non-CM cells are CF. These are traditionally responsible for the maintenance of the structural integrity of the heart through regulation and turnover of the ECM. Strictly-controlled production and secretion of proteins, such as collagens, fibronectin, matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinases (TIMPs), form a highly organised three-dimensional network surrounding myocytes and allow for mechanical force distribution throughout the myocardium.14 CF are cells of mesenchymal origin, but arise also from the fibrocytes, bone marrow-derived cells in the neonatal and adult heart.15,16,17 The main features of CF are the lack of a basement membrane, distinguishing them from all other permanent cardiac cells; an extensive Golgi apparatus; a relatively large endoplasmic reticulum, which underpins their role in protein synthesis and secretion; and their flat, spindle-shaped morphology with multiple filopodia originating from the main cell body.4

Under pathological stress, the resting fibroblast transdifferentiates into myofibroblast, expressing characteristics of smooth muscle cells and an enhanced capability for migration and tissue invasion.18,19,20 Moreover, myofibroblasts have been shown to originate from alternative cellular sources, including the local mesenchymal tissue, smooth muscle cells, vascular pericytes, a myeloid lineage, and fibrocytes.21,22 To date, the precise contribution of each cellular source to the myofibroblast population is poorly understood, but one hypothesis is that the transformation of differential cellular sources into myofibroblasts accounts for the manifestation of different forms of fibrosis (chronic versus acute).5 Several humoral factors can affect fibroblast activation and secretion of ECM proteins as well as their differentiation into myofibroblasts, including angiotensin II (AngII), endothelin 1 (ET-1), transforming growth factor- (TGF- ), fibroblast growth factor 2 (FGF2), and insulin-like growth factor-1 (IGF-1).17,23,24,25 Myofibroblasts play an important role in reparative healing of the myocardium following tissue damage.26 However, imbalanced myofibroblast activity results in interstitial fibrosis, ventricular stiffening, remodelling and failure.27 An important therapeutic consideration is the degree to which cardiac fibrosis is reversible and whether myofibroblasts can undergo senescence and apoptosis or dedifferentiate back to their original cell type.5 There is evidence that two weeks after myocardial infarction about a third of myofibroblasts undergo apoptosis; nevertheless, the fate of the remaining cells remains in question.28 The current research for fibrosis is directed at understanding and inhibiting signalling pathways that regulate myofibroblast transformation.

As with CM, fibroblasts also participate in mechano-electrical signalling which accounts for changes in the contractile function of the heart and arrhythmiogenicity in response to cardiac load alterations.13

Endothelium

The endothelial cells (EC) form the inner lining of blood vessels and as recently as the first half of the 20th century were viewed simply as barriers of blood flow. Today, endothelium has been recognised as a dynamic organ with complex biological functions, including the control of vascular permeability, the vasomotor control of coronary arteries, the regulation of haemostasis, immune responses and angiogenesis. The EC release nitric oxide, ET-1, AngII, prostaglandins, pro- and anticoagulant factors and growth factors that can affect the myocardial and vascular function.29 Furthermore, endothelium plays an important role in the regulation of heart size.30 There is evidence that the increase in myocardial vasculature is not only supportive of CM hypertrophy, but may actually induce the relevant process.31 Several studies support the notion that an increase in the capillary density is important for the development of physiological cardiac hypertrophy, whereas a reduction of the vascular bed size contributes to HF decompensation.32,33,34

Loading Simple Education