CARDIOMYOCYTE-FIBROBLAST COMMUNICATION

1. Under biomechanical overload, cardiac fibroblasts and myocytes respond to an altered environment via multiple mechanisms including integrin-extracellular matrix interactions and renin-angiotensin-aldosterone axis activation. Cardiac fibroblasts increase synthesis of matrix proteins and secrete a variety of paracrine factors that can stimulate myocyte hypertrophy. Cardiac myocytes similarly respond by secreting a conglomerate of factors. Hormones such as TGFβ1, FGF2, and the IL-6 family members LIF and CT-1 have all been implicated in this bidirectional fibroblast-myocyte hormonal crosstalk.
F2.medium

2.The IL33/ST2 system in the heart. The IL-33/ST2 system is a recently described cardiac fibroblast-myocyte signaling system. This signaling pathway serves an antihypertrophic and cardioprotective mechanism in the face of biomechanical overload. IL-33 is produced by mechanically loaded cardiac fibroblasts and is possibly inactivated by caspases. Extracellular IL-33 may bind to a soluble “decoy” form of its receptor, sST2, and be removed from the biologically available pool, or it may bind a transmembrane form, ST2L, on the surface of cardiac myocytes. In the face of prohypertrophic stimuli in vitro or pressure overload in vivo, IL-33 appears to confer antihypertrophic and antifibrotic properties to the myocardium.
F3.medium

CELL SIGNALLING IN THE HEART

                                                   DEFINITION

Communication between cells can be clearly defined as – ways in which living cells of an organism communicate with one another by-

 direct contact between cells

 chemical signals carried by neurotransmitter substances

 hormones

 cyclic AMP (ADENOSINE MONOPHOSPHATE)

                                                               TYPES

The different types of short distance cell – cell communication can be outlined as –

ENDOCRINE- Hormones are involved as (target cells) that is distant from synthesis site.

PARACRINE- Mediated by neurotransmitters by transmitting nerve impulses which regulate development at a short range meaning that cells must be in close proximity with one another.

AUTOCRINE- cells respond to substances which they release and linked with specific growth factors  (tumor cells) which stimulate unregulated, proliferation of themselves as well as adjacent non tumor cells.

Diagrams can be useful in further visual understanding of this topic…………

Cardiomyocytes  communication  involves-
1.  the secretion of autocrine factors
2.cell-cell propagation of depolarization fronts
3.physical association via gap junctions and adhesion complexes.

Based on the three types of communication,

 

1.Autocrine factors-

Autocrine communications are carried out by rich panoply of myocyte-secreted factors that include  leptin, FGF and TGFβ family members, midkine, hepatocyte growth factor, endothelin-1, and SDF1α. The end result of secretion of these factors in the heart is then a combination of a cardiomyocyte-cardiomyocyte and cardiomyocyte-non-cardiomyocyte cell interactions.

2.Gap junctions-                                                        

Allow cell-cell communication via the passage of ions and small solutes between them .In the heart, gap junctions and gap junction proteins of the connexin family have been shown to play a crucial role in determining impulse conduction and the heart morphogenesis. -, creation of the ability to functional diversity in gap junctions. Cardiac myocytes are involved in multiple connexin expression, regulation, trafficking and turnover and modulation of the channels ( importance of communication in development).

Gap junction remodeling-

Includes alteration in the expression and phosphorylation of specific connexinsand lateralization of the gap junction from the intercalated disc. This results in altered impulse conduction, but may also include  undefined, effects on cell-cell communication. Thus, not enough is currently known to prove or disprove the involvement of gap junction communications in myocardial hypertrophy.

BE SURE TO NOTE
The developmental abnormalities associated with the loss of specific connexins during heart embryogenesis have been attributed, to the role of gap junctions in the neural crest and neural tube. In addition, gap junctions in the proepicardium are purported to play a role in coronary development and patterning.

3.ADHESION COMPLEXES-

Adhesion complex communications involve intracellular signaling cascades that are triggered by cell-cell or cell-matrix engagement of specific proteins in these complexes.Alter myocardial responses to growth factors thereby modulating cardiac growth and hypertrophy.
It is also involved in connecting matrix adhesion to the intracellular cytoskeleton and in preservation of intercalated disc structure including organization of gap junctions and the distribution of connexin-43.

 

 

Source : http://www.ncbi.nlm.nih.gov/books/NBK21517/
 
               http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2941440/