IN-SMC

SMOOTH MUSCLE CELL TRANSCRIPTOMICS AND INFECTIOUS AGENTS

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 Obiettivo del progetto (Objective)

'A critical event in the formation of mature atherosclerotic plaque is migration of smooth muscle cells (SMCs) from the media to the intima, where they produce extra-cellular matrix (ECM) proteins, forming a fibrous cap above the pro-inflammatory and lipid core. SMC are highly plastic, and can alter their state of differentiation in response to environmental cues. Intimal SMC display pro-inflammatory properties, in that expression of the adhesion molecule P-selectin and cytokines are up-regulated and NFkB is activated. It is not explicitly known what triggers the pro-inflammatory phenotype of SMCs. We propose to utilize human carotid atheroma-derived SMC from endarterectomy specimens to identify the molecular basis of the pro-inflammatory phenotype of SMC in atherosclerosis via transcriptome analysis. Determining the specific gene expression pattern of SMCs in atherosclerotic plaques as well as in healthy tissue helps in gaining a better understanding of the plaque formation process. Since the oral cavity is well vascularized, we also hypothesize that infection in this site provides a direct route to the bloodstream and might contribute to plaque inflammation and changes in SMC responses. We will study whether biological samples from human periapical abscesses can induce inflammatory gene expression in SMC by using aspirates of bacteria from lesions of periodontal infection (containing bacteria such as Actinobacillus actinomycetemcomitans or Porhyromonas gingivalis) as well as contents of periapical abscesses from dental patients. The study of such pro-inflammatory events might provide insights into the development and/or destabilization of atherosclerotic plaque. The strong merit of the proposed study is the use of relevant human tissues which increases the translational value of the research and the possibility to understand human disease.'

Introduzione (Teaser)

A European study set out to understand how atherosclerosis is associated with inflammation. Researchers discovered a novel role of oral bacteria in activating plaque smooth muscle cells (SMCs) and initiating inflammation.

Descrizione progetto (Article)

The formation of atherosclerotic plaques is the hallmark of coronary heart disease. They build up on the inner walls of the arteries of the heart following the migration of SMCs and the production of extracellular matrix (ECM) components. These pro-inflammatory events recruit immune cells to the plaque causing severe inflammation and thrombosis.

However, the precise molecular mechanisms responsible for transforming a silent atheroma into a life-threatening plaque remain unknown. Based on the theory that inflammation is the main trigger, the EU-funded 'Smooth muscle cell transcriptomics and infectious agents' (IN-SMC) project set out to unveil the events that lead to inflammation. The work focused mainly on the changes in SMCs and the role of oral bacteria in inducing inflammatory gene expression.

In this context, scientists isolated SMCs from atherotic plaques and compared their gene expression with healthy cells. They found that SMCs had increased protein metabolism but reduced lipid metabolism. Additionally, bacteria were identified in patient dental abscesses such as Porhyromonas gingivalis. Aspirates from lesions of periodontal infection stimulated a higher cytokine production in SMCs, indicating the capacity of oral bacteria to activate SMC directly.

The results of the IN-SMC study demonstrate the role of oral bacteria on plaque stability and shed light into the process of plaque formation. The identification of the signalling pathways altered in SMCs could form the basis for the design of future therapeutic interventions.