Limits...
Natriuretic Peptide Signaling via Guanylyl Cyclase (GC)-A: An Endogenous Protective Mechanism of the Heart.

Kishimoto I, Tokudome T, Horio T, Garbers DL, Nakao K, Kangawa K - Curr Cardiol Rev (2009)

Bottom Line: These results suggest that the actions of a local cardiac ANP/BNP-GC-A system are essential for maintenance of normal cardiac architecture.In addition, GC-A was shown to exert its cardioprotective effects by inhibiting angiotensin II-induced hypertrophic signaling, and recent evidence suggests that regulator of G protein signaling (RGS) subtype 4 is involved in the GC-A-mediated inhibition of Galphaq-coupled hypertrophic signal transduction.Furthermore, several different groups have reported that functional mutations in the promoter region of the human GC-A gene are associated with essential hypertension and ventricular hypertrophy.

View Article: PubMed Central - PubMed

Affiliation: National Cardiovascular Center, Research Institute 5-7-1 Fujishiro-dai Suita City Osaka 565-8565, Japan.

ABSTRACT
Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones, secretions of which are markedly upregulated during cardiac failure, making their plasma levels clinically useful diagnostic markers. ANP and BNP exert potent diuretic, natriuretic and vasorelaxant effects, which are mediated via their common receptor, guanylyl cyclase (GC)-A (also called natriuretic peptide receptor (NPR)-A). Mice deficient for GC-A are mildly hypertensive and show marked cardiac hypertrophy and fibrosis that is disproportionately severe, given their modestly higher blood pressure. Indeed, the cardiac hypertrophy seen in these mice is enhanced in a blood pressure-independent manner and is suppressed by cardiomyocyte-specific overexpression of GC-A. These results suggest that the actions of a local cardiac ANP/BNP-GC-A system are essential for maintenance of normal cardiac architecture. In addition, GC-A was shown to exert its cardioprotective effects by inhibiting angiotensin II-induced hypertrophic signaling, and recent evidence suggests that regulator of G protein signaling (RGS) subtype 4 is involved in the GC-A-mediated inhibition of Galphaq-coupled hypertrophic signal transduction. Furthermore, several different groups have reported that functional mutations in the promoter region of the human GC-A gene are associated with essential hypertension and ventricular hypertrophy. These findings suggest that endogenous GC-A protects the heart from pathological hypertrophic stimuli, and that humans who express only low levels of GC-A are genetically predisposed to cardiac remodeling and hypertension.

No MeSH data available.


Related in: MedlinePlus

The patients with GC-A gene mutation are susceptible to cardiovascular diseases. These patients are resistant to ANP/BNP-mediated counter-regulation of Gαq signaling and are therefore more susceptible to cardiovascular diseases such as hypertension and cardiac hypertrophy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2803288&req=5

Figure 6: The patients with GC-A gene mutation are susceptible to cardiovascular diseases. These patients are resistant to ANP/BNP-mediated counter-regulation of Gαq signaling and are therefore more susceptible to cardiovascular diseases such as hypertension and cardiac hypertrophy.

Mentions: Collectively, the findings summarized in this section suggest that people carrying the certain variants of human GC-A gene are more susceptible to cardiovascular diseases such as hypertension and cardiac hypertrophy than those who do not, possibly because they are resistant to the counter-regulation of Gαq signaling by ANP/BNP (Fig. (6)).


Natriuretic Peptide Signaling via Guanylyl Cyclase (GC)-A: An Endogenous Protective Mechanism of the Heart.

Kishimoto I, Tokudome T, Horio T, Garbers DL, Nakao K, Kangawa K - Curr Cardiol Rev (2009)

The patients with GC-A gene mutation are susceptible to cardiovascular diseases. These patients are resistant to ANP/BNP-mediated counter-regulation of Gαq signaling and are therefore more susceptible to cardiovascular diseases such as hypertension and cardiac hypertrophy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2803288&req=5

Figure 6: The patients with GC-A gene mutation are susceptible to cardiovascular diseases. These patients are resistant to ANP/BNP-mediated counter-regulation of Gαq signaling and are therefore more susceptible to cardiovascular diseases such as hypertension and cardiac hypertrophy.
Mentions: Collectively, the findings summarized in this section suggest that people carrying the certain variants of human GC-A gene are more susceptible to cardiovascular diseases such as hypertension and cardiac hypertrophy than those who do not, possibly because they are resistant to the counter-regulation of Gαq signaling by ANP/BNP (Fig. (6)).

Bottom Line: These results suggest that the actions of a local cardiac ANP/BNP-GC-A system are essential for maintenance of normal cardiac architecture.In addition, GC-A was shown to exert its cardioprotective effects by inhibiting angiotensin II-induced hypertrophic signaling, and recent evidence suggests that regulator of G protein signaling (RGS) subtype 4 is involved in the GC-A-mediated inhibition of Galphaq-coupled hypertrophic signal transduction.Furthermore, several different groups have reported that functional mutations in the promoter region of the human GC-A gene are associated with essential hypertension and ventricular hypertrophy.

View Article: PubMed Central - PubMed

Affiliation: National Cardiovascular Center, Research Institute 5-7-1 Fujishiro-dai Suita City Osaka 565-8565, Japan.

ABSTRACT
Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones, secretions of which are markedly upregulated during cardiac failure, making their plasma levels clinically useful diagnostic markers. ANP and BNP exert potent diuretic, natriuretic and vasorelaxant effects, which are mediated via their common receptor, guanylyl cyclase (GC)-A (also called natriuretic peptide receptor (NPR)-A). Mice deficient for GC-A are mildly hypertensive and show marked cardiac hypertrophy and fibrosis that is disproportionately severe, given their modestly higher blood pressure. Indeed, the cardiac hypertrophy seen in these mice is enhanced in a blood pressure-independent manner and is suppressed by cardiomyocyte-specific overexpression of GC-A. These results suggest that the actions of a local cardiac ANP/BNP-GC-A system are essential for maintenance of normal cardiac architecture. In addition, GC-A was shown to exert its cardioprotective effects by inhibiting angiotensin II-induced hypertrophic signaling, and recent evidence suggests that regulator of G protein signaling (RGS) subtype 4 is involved in the GC-A-mediated inhibition of Galphaq-coupled hypertrophic signal transduction. Furthermore, several different groups have reported that functional mutations in the promoter region of the human GC-A gene are associated with essential hypertension and ventricular hypertrophy. These findings suggest that endogenous GC-A protects the heart from pathological hypertrophic stimuli, and that humans who express only low levels of GC-A are genetically predisposed to cardiac remodeling and hypertension.

No MeSH data available.


Related in: MedlinePlus