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FGF21 and Cardiac Physiopathology.

Planavila A, Redondo-Angulo I, Villarroya F - Front Endocrinol (Lausanne) (2015)

Bottom Line: The heart is sensitive to the effects of FGF21, both systemic and locally generated, owing to the expression in cardiomyocytes of β-Klotho, the key co-receptor known to confer specific responsiveness to FGF21 action.In humans, circulating FGF21 levels are elevated in coronary heart disease and atherosclerosis, and are associated with a higher risk of cardiovascular events in patients with type 2 diabetes.These findings provide new insights into the role of FGF21 in the heart and may offer potential therapeutic strategies for cardiac disease.

View Article: PubMed Central - PubMed

Affiliation: Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona , Barcelona , Spain ; CIBER Fisitopatologia de la Obesidad y Nutrición, Instituto de Salud Carlos III , Barcelona , Spain.

ABSTRACT
The heart is not traditionally considered either a target or a site of fibroblast growth factor-21 (FGF21) production. However, recent findings indicate that FGF21 can act as a cardiomyokine; that is, it is produced by cardiac cells at significant levels and acts in an autocrine manner on the heart itself. The heart is sensitive to the effects of FGF21, both systemic and locally generated, owing to the expression in cardiomyocytes of β-Klotho, the key co-receptor known to confer specific responsiveness to FGF21 action. FGF21 has been demonstrated to protect against cardiac hypertrophy, cardiac inflammation, and oxidative stress. FGF21 expression in the heart is induced in response to cardiac insults, such as experimental cardiac hypertrophy and myocardial infarction in rodents, as well as in failing human hearts. Intracellular mechanisms involving PPARα and Sirt1 mediate transcriptional regulation of the FGF21 gene in response to exogenous stimuli. In humans, circulating FGF21 levels are elevated in coronary heart disease and atherosclerosis, and are associated with a higher risk of cardiovascular events in patients with type 2 diabetes. These findings provide new insights into the role of FGF21 in the heart and may offer potential therapeutic strategies for cardiac disease.

No MeSH data available.


Related in: MedlinePlus

The heart and FGF21 inter- and intra-organ communication. Several tissues in the organism are potential producers of FGF21. The main contributor to circulating levels of FGF21 is the liver (46) and, under most physiological settings, a minor role is played by the white and brown adipose tissues. After myocardial infarction, liver and white adipose tissue produce large amounts of FGF21. The heart also produces increased levels of FGF21 after cardiac insults, such as cardiac hypertrophy, oxidative stress, and diabetes, among others. The endocrine action of FGF21 released by the liver and possibly by adipose tissues, together with autocrine FGF21 originating in heart itself, may act to protect against cardiac damage. The extent to which the heart contributes to systemic FGF21 levels is not yet fully established.
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Figure 2: The heart and FGF21 inter- and intra-organ communication. Several tissues in the organism are potential producers of FGF21. The main contributor to circulating levels of FGF21 is the liver (46) and, under most physiological settings, a minor role is played by the white and brown adipose tissues. After myocardial infarction, liver and white adipose tissue produce large amounts of FGF21. The heart also produces increased levels of FGF21 after cardiac insults, such as cardiac hypertrophy, oxidative stress, and diabetes, among others. The endocrine action of FGF21 released by the liver and possibly by adipose tissues, together with autocrine FGF21 originating in heart itself, may act to protect against cardiac damage. The extent to which the heart contributes to systemic FGF21 levels is not yet fully established.

Mentions: In summary, in addition to the protective role exerted by systemic, circulating FGF21 on the heart, local secretion of FGF21 in the context of cardiac damage may serve as an endogenous, autoregulatory, cardioprotective signaling pathway. Thus, systemic or locally generated FGF21 acts on the myocardium, protecting it from cardiac injury (Figure 2).


FGF21 and Cardiac Physiopathology.

Planavila A, Redondo-Angulo I, Villarroya F - Front Endocrinol (Lausanne) (2015)

The heart and FGF21 inter- and intra-organ communication. Several tissues in the organism are potential producers of FGF21. The main contributor to circulating levels of FGF21 is the liver (46) and, under most physiological settings, a minor role is played by the white and brown adipose tissues. After myocardial infarction, liver and white adipose tissue produce large amounts of FGF21. The heart also produces increased levels of FGF21 after cardiac insults, such as cardiac hypertrophy, oxidative stress, and diabetes, among others. The endocrine action of FGF21 released by the liver and possibly by adipose tissues, together with autocrine FGF21 originating in heart itself, may act to protect against cardiac damage. The extent to which the heart contributes to systemic FGF21 levels is not yet fully established.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4553397&req=5

Figure 2: The heart and FGF21 inter- and intra-organ communication. Several tissues in the organism are potential producers of FGF21. The main contributor to circulating levels of FGF21 is the liver (46) and, under most physiological settings, a minor role is played by the white and brown adipose tissues. After myocardial infarction, liver and white adipose tissue produce large amounts of FGF21. The heart also produces increased levels of FGF21 after cardiac insults, such as cardiac hypertrophy, oxidative stress, and diabetes, among others. The endocrine action of FGF21 released by the liver and possibly by adipose tissues, together with autocrine FGF21 originating in heart itself, may act to protect against cardiac damage. The extent to which the heart contributes to systemic FGF21 levels is not yet fully established.
Mentions: In summary, in addition to the protective role exerted by systemic, circulating FGF21 on the heart, local secretion of FGF21 in the context of cardiac damage may serve as an endogenous, autoregulatory, cardioprotective signaling pathway. Thus, systemic or locally generated FGF21 acts on the myocardium, protecting it from cardiac injury (Figure 2).

Bottom Line: The heart is sensitive to the effects of FGF21, both systemic and locally generated, owing to the expression in cardiomyocytes of β-Klotho, the key co-receptor known to confer specific responsiveness to FGF21 action.In humans, circulating FGF21 levels are elevated in coronary heart disease and atherosclerosis, and are associated with a higher risk of cardiovascular events in patients with type 2 diabetes.These findings provide new insights into the role of FGF21 in the heart and may offer potential therapeutic strategies for cardiac disease.

View Article: PubMed Central - PubMed

Affiliation: Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona , Barcelona , Spain ; CIBER Fisitopatologia de la Obesidad y Nutrición, Instituto de Salud Carlos III , Barcelona , Spain.

ABSTRACT
The heart is not traditionally considered either a target or a site of fibroblast growth factor-21 (FGF21) production. However, recent findings indicate that FGF21 can act as a cardiomyokine; that is, it is produced by cardiac cells at significant levels and acts in an autocrine manner on the heart itself. The heart is sensitive to the effects of FGF21, both systemic and locally generated, owing to the expression in cardiomyocytes of β-Klotho, the key co-receptor known to confer specific responsiveness to FGF21 action. FGF21 has been demonstrated to protect against cardiac hypertrophy, cardiac inflammation, and oxidative stress. FGF21 expression in the heart is induced in response to cardiac insults, such as experimental cardiac hypertrophy and myocardial infarction in rodents, as well as in failing human hearts. Intracellular mechanisms involving PPARα and Sirt1 mediate transcriptional regulation of the FGF21 gene in response to exogenous stimuli. In humans, circulating FGF21 levels are elevated in coronary heart disease and atherosclerosis, and are associated with a higher risk of cardiovascular events in patients with type 2 diabetes. These findings provide new insights into the role of FGF21 in the heart and may offer potential therapeutic strategies for cardiac disease.

No MeSH data available.


Related in: MedlinePlus