Review articleToll-like receptor-4 signaling pathway in aorta aging and diseases: “its double nature”

- The TLR-4 signaling pathway is involved in aorta health and diseases, as aneurysms.
- Low/or high levels of PAMPs or DAMPs result in short/or sustained TLR4 activation.
- Aorta protection, homeostasis and repair are the result of a short TLR4 activation.
- Thoracic aorta aneurysms seem to be the result of a sustained TLR-4 activation.
- Agonists or antagonists of TLR-4 pathway could be treatments for aortic diseases.

Recent advances in the field of innate immunity have revealed a complex role of innate immune signaling pathways in both tissue homeostasis and disease. Among them, the Toll-like receptor 4 (TLR-4) pathways has been linked to various pathophysiological conditions, such as cardiovascular diseases (CVDs). This has been interrogated by developing multiple laboratory tools that have shown in animal models and clinical conditions, the involvement of the TLR-4 signaling pathway in the pathophysiology of different CVDs, such as atherosclerosis, ischemic heart disease, heart failure, ischemia-reperfusion injury and aorta aneurysm. Among these, aorta aneurysm, a very complex pathological condition with uncertain etiology and fatal complications (i.e. dissection and rupture), has been associated with the occurrence of high risk cardiovascular conditions, including thrombosis and embolism. In this review, we discuss the possible role of TLR-4 signaling pathway in the development of aorta aneurysm, considering the emerging evidence from ongoing investigations. Our message is that emphasizing the role of TLR-4 signaling pathway in aorta aneurysm may serve as a starting point for future studies, leading to a better understanding of the pathophysiological basis and perhaps the effective treatment of this difficult human disease.

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