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 one’s 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 isn’t 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 don’t 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 I’m not sure if you covered this as part of your cell stuff, I can go back and add

more if you didn’t.

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 doesn’t 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 don’t 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 isn’t 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.pdf

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%2F1755-1536-5-15&token2=exp=1454457621~acl=%2Fstatic%2Fpdf

%2F42%2Fart%25253A10.1186%25252F1755-1536-5-

15.pdf*~hmac=025a5558fc685c14166ae3275ddccb8042232a39be9416793f85bb57ca83

2d06 this link could also be useful for you if you need more info

4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946433/

5.