Abstract
We will summarize the data we have obtained in human carotid artery concerning the organization of an extended local renin angiotensin aldosterone system and its variations at different stages of atheroma. In a system view, we propose a model where concomitant increase in angiotensin and glucocorticoid signaling is induced and amplified in VSMC while vascular smooth muscle cells transdifferentiate toward a lipid storing phenotype.
Highlights
Systems are complex objects linking several single components which, associated in a certain way with multiple relationships perform a specific task
As in other vascular models, the mRNA for AGT can be detected in the medial vascular smooth muscle cells (VSMC) from human carotid arteries and significant amounts of AGT protein can be detected in the arterial wall [29, 30]
Thanks to the availability of public transcriptomic data, preliminary results obtained in different normal tissues from human confirm the hypothesis that a description and classification of tissue specific organization of tRAAS according to mRNA coexpression of its components may be achieved
Summary
Systems are complex objects linking several single components which, associated in a certain way with multiple relationships perform a specific task. Blood pressure or blood flow, glycemia, temperature, and most functionally relevant parameters measured or assessed by the physicians appear only at a high level of biological integration These parameters result from numerous molecular events which take place at the cellular level in a large variety of tissues and are coordinated through regulatory networks. The amount of almost each transcribed RNA and all mRNA and this can be related to chromatin structure and DNA binding proteins (ENCODE) This new knowledge allows a new paradigm where, instead of looking for a single component and its involvement in a specific step of a mechanism or pathway, it is possible to check among all of the possible known components and their interactions, those that do take place in a specific instance at a specific time point. We will summarize according to this point of view some of the data we have obtained concerning the organization of the RAAS system in our study model of human carotid atheroma (Figure 1)
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