Angiotensin II (ANGII) is a
hormone that can cause problematic changes in the heart such as inflammation, thickening
of the walls of the heart, high blood pressure and fibrosis (excessive scar
tissue). One pathological change the lab
I work for studies is cardiac fibrosis (excessive scar tissue) caused by
angiotensin II. The heart consists mostly of two types of cells: myocytes and
fibroblasts. Fibroblasts are cells in connective tissue that are involved in
tissue repair. They are located between
myocytes and contribute to the structure and mechanical properties of the
heart. Fibroblasts have a receptor
called angiotensin type I receptor (AT1R). When Angiotensin II binds to the angiotensin
type I receptor, a signaling pathway is activated in the cardiac fibroblasts. This leads to an increase production of cytokines
in the fibroblast. Cytokines are signal
proteins. One cytokine that is made is the transforming growth factor beta (TGFβ). TGFβ is secreted from the cardiac fibroblast
to recruit other fibroblasts to this area in the heart. The fibroblasts also secrete extracellular
matrix (complex network of proteins), that are rich in collagen. This creates a scar. Many types of immune cells are recruited to
this area too. This cascade of events
leads to fibrosis (excessive scar tissue).
Below are two pictures of a section of a mouse heart that has
angiotensin II induced fibrosis from my lab.
The arrows point to white blood cells (red nuclei) in the fibrotic
area of a mouse heart.
I work for a lab that looks at the
effects certain drugs have on the angiotensin II signal pathway in the
heart. We implant pumps into mice that
release angiotensin II and expose them to different drugs by injections. Then we look at cardiac fibrosis by staining sections of the mice’s hearts (as seen in the pictures above). We also look at the quantity and type of
immune cells in the heart and venous blood from the mice. I have many questions from the experiments my
lab has done such as: What is the mechanism that triggers the immune response
in the fibrotic areas of the heart?
Where do the immune cells come from (lymph nodes, bone marrow)? Where do the fibroblasts come from that are
recruited by the cytokine TGFβ (bone marrow, other surrounding tissues next
to the heart)?
Sources:
Leask A. TGFβ,
cardiac fibroblasts and the fibrotic response.
Cardiovascular Research 2007;74:207-212.
Mehta P, Criendling K. Angiotensin II cell signaling: physiological
and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol 2007;292:C82-C97.
Mckinsey lab in the division of
cardiology.
It was very interesting to see the effects of Angiotensin II in the vasculature as well as in the heart. Hopefully, this will help reinforce the importance of blood pressure management, not just by physicians (who already know this) but also by patients and educators, Fortunately, we have been able to manipulate the renin-angiotensin-aldosterone system and use it to our advantage (http://upload.wikimedia.org/wikipedia/commons/a/a2/Renin-angiotensin-aldosterone_system.png). Angiotensinogen is converted to Angiotensin I, which is converted to Angiotensin II by ACE (angiotensin-converting enzyme) in the lung. When angiotensin II binds to the receptors, it causes the effects, including secretion of aldosterone from the adrenal cortex.
ReplyDeleteWhat pharmacologists have done is take advantage of the RAAS. We have ACE inhibitors (lisinopril, captopril), calcium-channel blockers (verapamil, amilodipine, and nefidipine) angiotensin-receptors blockers (losartan) and even aldosterone blockers (spironolactone).
However, the first-line effort is lifestyle modifications. Essentially, reduce the intake of salt, alcohol, and fatty foods, and engage in stress-relieving activities such as cardiovascular exercise (jogging) meditation, yoga, or tai chi.
Angiotensin II is an octapeptide that produced from angiotensin I after the removal of two amino acids at the C-terminal by angiotensin-converting enzyme (ACE). Angiotensin II is mediated by AT1 and AT2 receptors, Angiotensin II Acetate
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