Proteomics and ex vivo plaque culture identify the insulin-like growth factor axis as a potential regulator of matrix remodelling in carotid plaques.
This study suggests that the insulin-like growth factor axis may regulate the stability of atherosclerotic plaques, but further research is needed to confirm these findings in clinical settings.
Where it sits
this study against the rest of the mgf (mechano growth factor) corpusSummary and findings
This study examined the proteomic profiles of carotid atherosclerotic plaques and the effects of insulin-like growth factor 1 (IGF-1) on plaque stability. A total of 76 plaques and 8 non-atherosclerotic artery segments were analyzed, with 22 plaques cultured ex vivo for 22 days. The findings suggest that the IGF axis may play a role in regulating plaque stability.
Abstract
<h4>Background and aims</h4>Rupture of carotid atherosclerotic plaques is a significant cause of stroke. We have previously analyzed 21 plaques by mass spectrometry and reported differing proteomic profiles between morphologically unstable (rupture-prone) and stable plaques. This expanded dataset includes additional carotid plaques as well as non-atherosclerotic arteries, allowing comparison with control tissue. Additionally, the role of insulin-like growth factor 1 (IGF-1) signaling in plaque stability was investigated with ex vivo cultured plaques.<h4>Methods</h4>Plaques (n = 76) and non-atherosclerotic superior thyroid artery segments (n = 8) were retrieved from carotid endarterectomies. Additionally, 22 plaques were cultured ex vivo for 22 days to examine IGF-1 signaling effects. Proteins were analyzed by liquid chromatography-mass spectrometry.<h4>Results</h4>Mass spectrometric proteome analysis identified three clusters associated with two different plaque phenotypes (type A and type B) and non-atherosclerotic arteries. 2608 proteins were differentially abundant in plaques compared to non-atherosclerotic arteries. 1315 proteins were differentially abundant between plaque types A and B. Proteins linked to IGF transport and binding, particularly IGF-binding proteins, were more abundant in plaques compared to non-atherosclerotic arteries, and in type B compared to type A plaques. IGF-1, IGF-2 and the IGF-1 receptor were more abundant in type B plaques, whereas the IGF-2 receptor was more abundant in type A. IGF-1 treatment of ex vivo plaques decreased matrix metalloproteinase 9 and increased collagen type XXI, consistent with increased plaque stability.<h4>Conclusions</h4>Proteomic analyses of atherosclerotic plaques, and ex vivo plaques cultured with IGF-1, reveal the IGF axis as a potential regulator of human atherosclerotic plaque stability.
Background
The paper addresses the biological question of how the insulin-like growth factor (IGF) axis may influence matrix remodeling in carotid plaques, which is relevant for understanding atherosclerosis. Prior research has indicated that matrix remodeling plays a crucial role in plaque stability and cardiovascular risk. This study aims to elucidate the specific mechanisms by which the IGF axis may regulate these processes.
Methods
The study design includes proteomics and ex vivo culture of carotid plaques, although specific details regarding the population, sample size, and duration are not reported in the abstract. The primary and secondary outcome measures are also not specified.
Results
Not reported in abstract.
Interpretation
Without specific numeric findings or effect sizes reported, it is challenging to compare this study's results with prior literature or assess the clinical significance of the findings. The lack of detailed outcomes limits the ability to draw firm conclusions about the implications for practice.
Key findings
- Not reported in abstract.
- Not reported in abstract.
- Not reported in abstract.
Limitations
- Not reported in abstract.
- Not reported in abstract.