The NO signalling pathway in aortic aneurysm and dissection.

Area of Science:

• Cardiovascular Research
• Molecular Medicine
• Genetics

Background:

• Thoracic aortic aneurysm (TAA), often linked to Marfan syndrome, involves progressive aortic dilation and dissection.
• Current treatments for TAA are limited, with surgery being the only definitive option, highlighting the need for novel therapeutic strategies.
• Nitric oxide (NO) signaling dysregulation is increasingly recognized as a key factor in TAA pathogenesis.

Purpose of the Study:

• To elucidate the mechanisms by which NO signaling dysregulation contributes to TAA, with a focus on Marfan syndrome.
• To identify novel mediators and potential biomarkers associated with Marfan syndrome-related TAA.
• To evaluate the therapeutic potential of targeting specific NO pathway components in TAA.

Main Methods:

• Review of recent studies on NO signaling in TAA and Marfan syndrome.
• Identification and discussion of emerging Marfan syndrome mediators.
• Analysis of pharmacological inhibition of iNOS, sGC, and PRKG1 in preclinical models of Marfan syndrome-associated aortopathy.

Main Results:

• NO signaling dysregulation is a central mechanism in the development of TAA, particularly in Marfan syndrome.
• New mediators linked to pathway overactivation in Marfan syndrome have been identified as potential biomarkers.
• Pharmacological inhibition of inducible nitric oxide synthase (iNOS), soluble guanylate cyclase (sGC), and protein kinase G1 (PRKG1) demonstrated efficacy in reversing aortopathy in Marfan syndrome mouse models.

Conclusions:

• Understanding NO signaling pathways is crucial for developing new treatments for TAA.
• Targeting iNOS, sGC, and PRKG1 represents a promising therapeutic strategy for TAA, especially in Marfan syndrome.
• These targets warrant further investigation and are strong candidates for clinical trials in TAA patients.