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Flashcards in Cardiac Cell Biology Deck (28)
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1
Q

Cardiac tissue

A

consists of essentially three cell types:

(i) cardiac myocytes (syn = cardiomyocyte = CMs),
(ii) endothelial cells including a specialized layer of cells known as the endocardium as well as the inner linings of BVs and
(iii) “cardiac” fibroblasts (CFs).

2
Q

The Cardiac Myocyte: Similarities to Skeletal Muscle

A
- Each cardiomyocyte is surrounded by
a basal lamina.
- Cardiomyocytes are striated.
- Mechanism of contraction and types of
contractile proteins are similar
3
Q

The Cardiac Myocyte: Differences to Skeletal Muscle (Gross)

A

Unlike skeletal muscle which is voluntary in function, cardiac muscle is involuntary.

4
Q

The Cardiac Myocyte: Differences to Skeletal Muscle (Light Microscope Level)

A
  • Cardiac myocytes are smaller, ~15 micrometers x 100 micrometers (not mm).
  • The nucleus is centrally located. There are 1 or
    2 (sometimes 3) nuclei per cell, not 100s.
  • Cardiac cells bifurcate, whereas
    skeletal cells branch only when they’re sick.
  • Cardiac tissue is very highly vascularized, and, CMs are chock full of mitochondria.
  • Intercalated discs are specialized intercellular structures that are present only in cardiomyocytes.
5
Q

The Cardiac Myocyte: Differences to Skeletal Muscle (Electron Microscope Level)

A

Cardiac myocytes are highly enriched in glycogen, and mitochondria.
- This is to satisfy continual energy demand.

6
Q

Intercalated Discs: What is it?

A

Intercellular attachments enable cardiac myocytes to work together, as if they were part of a “syncytium” (which they are not). In attaching cardiac myocytes together, discs on adjacent cells appear to form a ‘staircase’ across the myocardium.

7
Q

Each intercalated disc has two ________-________ parts: a ________ part and a ______ part

A

Each intercalated disc has two perpendicularly-arranged parts: a transverse part and a lateral part.

8
Q

The transverse part of an intercalated disc

A

Transverse Part that transmits contractile force. This
component, which is essentially a ‘half Z-band’, consists of:
- A fascia adherens, which (unlike zonula adherens does
not completely encircle cell).
- desmosomes (syn. macula adherens)
- Actin (thin) filaments butt into these half-Z bands, akin to zonula adherens in junctional complexes. The major protein in the fascia adherins is N-cadherin.

9
Q

The lateral part of an intercalated disc

A

The lateral part transmits cell-to-cell signals.
- Signaling is accomplished via nexuses (syn. gap junctions, connexons), which function to maintain rhythmicity to heartbeat. Each connexon has 6 connexin proteins. Desmosomes are also in the lateral component.

10
Q

Cardiac Myocytes are _______ than in the ventricles, with ______ sacromeric structure.

A

Cardiac myocytes are smaller than in the ventricle, with less sarcomeric structure.

11
Q

SA & AV Nodes

A

Located in the R. atrium.

  • Node myocytes are small, embedded in dense connective tissue.
  • Cells of the SA and AV nodes have few myofibriles & are adapted for impulse propagation.
  • By contrast, the AV Bundle of His contains large Purkinje myocytes that have few myofibrils and copious glycogen with inconspicuous intercalated discs.
12
Q

Development of Purkinje “fibers”

A

Endothelial cells within young coronary arteries secrete endothelin, which causes nearby cardiac myocytes to differentiate into Purkinje cells.

13
Q

Endocardium

A
  • The innery lining of the heart that lines the lumens of the ventricles.
  • Composed of endothelial cells (simple squamous epithelium that lines all chambers of the heart and is continuous with the endothelial lining the entire vascular system.
14
Q

What is the most abundant cell type in the heart?

A

Cardiac Fibroblasts

15
Q

What is the major fuel for the cardiac myocyte?

A

Triglycerides (Stored in membrane-bound lipid droplets near the nucleus)

16
Q

Mitochondria concentration: cardiac vs. skeletal myocytes

A

Mitochondria is 20-fold greater in cardiomyocytes when compares to that of skeletal myocytes per volume (40% vs. 2%).
These attributes enable the heart to function as a continuously aerobic organ.

17
Q

What are the diagnostic differences between Cardiac and Skeletal Myocytes?

A

Cardiac:

  • MB isoforms of creatine kinase (MB-CK): occupies of the M-line of cardiac muscle. Diagnostic for MI’s as it is present in high levels in the serum after a heart attack, due to cardiac myocyte death.
  • Cardiac Troponin-I (cTnI): Another diagnostic of MI

Skeletal:
- Occupies the M-line of skeletal muscles. High levels of MM-creatine kinase (MM-CK), which occupies the M-line of skeletal muscle, indicates muscular dystrophy.

18
Q

How is heartbeat regulated?

A

Besides intrinsic control, the vagus nerve (X), and autonomic nerves only control rate of contraction, not the contraction itself.

19
Q

Chronology of a Heart Attack

A
  1. Myocyte Death: Starts immediately, apoptosis/necrosis begin. MB-CK & cTnI released.
  2. Inflammation: Starts ~ 15 hours later, accompanied by complement activation/cytokine release.
  3. Wound Healing: Starts after 2-3 days, mediated by cardiac fibroblasts, which make and secrete collagen proteins, ultimately (by day 5) creating a scar.
  4. Angiogenesis (new blood vessel formation): Starts 2-4 days, induced by VEGF/FGF.
  5. Scar Formation is mediated by formation of collagen cross-links mediated by lysyl oxidase.
20
Q

Is Cardiac Myocyte Regeneration Possible?

A

A lot of research has been done into finding ways to replace cardiac myocytes due to heart related illness (MI).
At this moment the regeneration of myocytes is not sufficient to overcome the loss of cardiac myocytes and contractile function of after a heart attack.

21
Q

Approaches to trying to replace cardiac myocytes and coronary vessels.

A
  1. Skeletal Myoblats (transplanted)
  2. Cardiac Fibroblasts (CFs, endogenous)
  3. Mobilization of Existing Healthy Cardiac Myocytes (endogenous)
  4. Mobilization of Adult Heart Stem Cells (endogenous)
  5. Transplant of Adult Heart Stem Cells
  6. Transplant of Bone Marrow Cells
  7. Transplantation of Cardiomyocytes derived from pluripotent stem cells.
22
Q

Can Skeletal Myoblasts to re-muscularize the injured heart?

A

No.

Abandoned die to inefficacy and arrhythmias.

23
Q

Can cardiac fibroblasts to re-muscularize the injured heart?

A

No.
Fibroblasts cannot regenerate the heart, they create scars, and scars cannot contract.
cardiac fibroblasts double after infarction, cardiac myocytes die after infarction.

24
Q

Can mobilization of pre-existing healthy cardiac myocytes re-muscularize the injured heart?

A

Maybe.
In these instances, CM proliferation was induced by interventions such as (i) inhibiting the p38 MAP kinase pathway, or by (ii) treating the heart with pro-proliferative proteins such as neuregulin.
Yet, no results have been posted. (Bad Sign)

It is also being investigated whether inhibition o
f tumor suppressor proteins, which normally keep CMs
in a state of ‘replicative senescence” (i.e. G0 of the cell-cycle), can release the cell-cycle block, thereby permitting regeneration. However this could lead to cancer proliferation.

25
Q

Can mobilization of adult stem cells re-muscularize the injured heart?

A

No. But they could be mobilized to do so.
The adult stem cells are identified per expression of a stem cell marker termed c-Kit.
Treating the heart with drugs and/or growth factors could mobilize & expand these stem cells in their niches.

26
Q

Can c-Kit+ adult stem cells be transplanted to fix injured myocardium?

A

Maybe.

a. isolate c-Kit+ cells from R. atrial appendage or R IV septum via catheter.
b. Expand c-kit+ cells in culture
c. Transplant 2 million c-kit+ cells back into same patient.
d. Some function is restored & infarcted area is reduced, while “no harm is done” -> No harm is done due to the paracrine factors that cause a positive effect on the heart

27
Q

Can transplanted bone marror cells fix injured myocardium?

A

Maybe.
The idea is that bone marrow cells might migrate to the heart & take up residence as adult stem cells.
- You’d harvest bone marror from patient
- transplant into same patient via catheter
Results are probably due to the paracrine effect. But there is a modest increase in heart function.

28
Q

Can transplantation of cardiac myocytes derived from induced pluripotent cells (iPSCs) fix injured myocardium?

A

Yes.
iPSCs -> >200 different cell types
Generated via “reversal of aging”
- patient’s dermal fibroblasts/T-cells + 3-4 transcription factors -> iPSCs + cardiomyogenic growth factors -> cardiomyocytes -> transplant into same patient