Cardiovascular cGMP-generating systems in physiological and pathological conditions

Area of Science:

• Cardiovascular Physiology
• Molecular Signaling

Background:

• Cyclic GMP (cGMP) is a crucial intracellular messenger in animal signaling.
• In the heart, cGMP mediates interactions between different cell types.
• Nitric oxide (NO) and natriuretic peptides (NPs) are key cardiovascular regulators that increase cGMP via guanylate cyclases (GCs).

Purpose of the Study:

• To review recent concepts on NO/NPs-dependent control of heart function in vertebrates.
• To focus on cGMP-activated downstream signaling in health and disease.
• To highlight the reciprocal regulation between NO and NP pathways.

Main Methods:

• Review of existing literature on NO/NPs signaling in the heart.
• Analysis of the interaction between soluble (sGC) and particulate (pGC) guanylate cyclases.
• Examination of cGMP's role in cardiovascular homeostasis and pathology.

Main Results:

• NO and NPs activate distinct GC types (sGC and pGC, respectively), producing complementary cGMP effects.
• The NO and NP pathways exhibit heterologous feedback, modulating each other's activity.
• These cGMP signaling routes are critical in cardiovascular diseases, such as endothelial dysfunction, and influence myocardial remodeling.

Conclusions:

• Converging NO and NP signaling pathways are essential for heart function and adaptation.
• Dysregulation of these cGMP pathways contributes to cardiovascular pathology.
• Targeting these pathways offers potential therapeutic strategies for heart conditions.