Heart Muscle ECM

The connective tissue around the heart muscle has three layers, from
outer to inner these layers are the epimysium, the perimysium and the
endomysium. The endomysium is what contains the extracellular matrix
(ECM) which has much to do with how the cardiomyocytes (heart muscle
cells) interact with one another in their mission to beat blood through ones
system and during differentiation of the stem cells into myocardial cells.
Usually the ECM takes up more volume than the cells of its tissue, but this
isnt true in the heart where cardiac myocytes occupy more space and the
ECM is less abundant [4]. The extracellular matrix is produced by the
myocardial cells and the fibroblasts, which are most of the cells in the normal
heart. It is made of type I, III, and IV collagen, laminin, fibronectin, and
proteoglycans. Its structure in a healthy heart allows alignment so they
cardiomyocytes can act as a network of many cells that act as one.
Perhaps most important of the extracellular functions in the heart is
performed by the intercalated discs which are unique to heart muscle and
are what connect the numerous cells into one functional organ. In contrast
with skeletal muscle which has no such intercalated discs as they dont need
to all contract at the same time in order to work, in fact it would be bad if
they did in most cases. The discs are located on the Z line of the sarcomere
so they can link adjacent heart muscle units. Making up the discs are three
different types of cell junction; these are fascia adherens (anchor actin and
connect to the nearest sarcomere), desmosomes (bind intermediate

filaments in order to join cells together), and gap junctions (allow action
potentials to pass between cells so the entire organ will beat in time to pump
the blood correctly). Through these junctions between the cells the
intercalated discs let the action potential of the heart beat to flow through
the entire organ without stopping so it will be one smooth motion which is
important to the function of the heart [1]. There is much more on this
subject but Im not sure if you covered this as part of your cell stuff,
I can go back and add more if you didnt.
Collagen, common throughout the body, is also present in the heart,
mostly as type one and three. Disease can change the ratio of collagen
types and lead to the heart chambers stiffness even though changes in total
collagen concentration doesnt always lead to the same state [2]. This is a
problem because the heart needs to be flexible so it can move and pump
blood. Due to the uptake in cases of myocardial infarction this is particularly
important, because after a heart attack the heart will heal with
myofibroblasts. These cells dont make more muscle cells, instead they
produce an ECM around the affected area, allowing the heart as a whole to
keep its integrity but sacrificing its strength. In numbers this is represented
by 60% of the scar post heart attack to be collagen at day 21. Cardiac
fibroblasts are the primary source for all cardiac ECM proteins as well as
matrix metalloproteinases, which degrade ECM proteins, and their inhibitors.
The balance of these regulatory proteins is what maintains homeostasis
within the matrix [3].

Collagen may be the most common but it isnt the only important
protein in the heart, laminin for example is important as a basement
membrane protein that mainly functions by anchoring cells to the ECM and
has binding cites for other ECM proteins allowing cross-linking. Fibronectin
also has a role to play as it contains the infamous RGD sequence, it stabilizes
the rest of the ECM and shapes the cell and its movement
As mentioned above the ECM also has to do with differentiation of the
stem cells into myocardial cells. This has been previously proven by multiple
studies which would add cardiac progenitor cells to a cardiac
microenvironment which imitates the heart. After the addition the stem
cells would start to differentiate into heart cells. This means that the ECM
must play a role in how the cells will recognize their surroundings and
differentiate accordingly. This is further proved by a study done by Castaldo
et al. in which they took fibroblasts from healthy or diseased cardiac tissues
and used them to produce a layer of ECM proteins. Cardiac stem cells were
then added and although both ECMs kept the cells from entering apoptosis
only the ECM derived from the healthy fibroblasts stimulated proliferation
and migration [2].

1. http://www.hellenicjcardiol.com/archive/full_text/2012/5/2012_5_367.pd
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2. http://www.oapublishinglondon.com/article/1338#
3. http://download.springer.com/static/pdf/42/art
%253A10.1186%252F1755-1536-5-15.pdf?originUrl=http%3A%2F
%2Ffibrogenesis.biomedcentral.com%2Farticle%2F10.1186%2F17551536-5-15&token2=exp=1454457621~acl=%2Fstatic%2Fpdf
%2F42%2Fart%25253A10.1186%25252F1755-1536-515.pdf*~hmac=025a5558fc685c14166ae3275ddccb8042232a39be94
16793f85bb57ca832d06 this link could also be useful for you if you
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4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946433/
5.