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Updated: Jun 11, 2025
Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
Published on: September 15, 2017
Medin Induces Pro-Inflammatory Activation of Human Brain Vascular Smooth Muscle Cells
Background:
Medin is one of the most common amyloidogenic proteins and accumulates in the vasculature with aging. Vascular medin accumulation is associated with Alzheimer's disease, vascular dementia and aortic aneurysms. Medin impairs smooth muscle-dependent vasodilation in isolated human brain cerebral arteries. The role of medin in vascular smooth muscle (VSMC) activation is unknown. We aim to evaluate the effects of medin on human brain VSMC activation.
Methods:
VSMCs were exposed to physiologic doses of medin (0.5, 1 and 5 µM) without or with small molecule nuclear factor-κB (NFκB) inhibitor RO106-9920 (10 µM) for 20 hours. Polymerase chain reaction, Western blot/enzyme-linked immunosorbent assay were used to quantify gene and protein expressions/secretions, respectively, of pro-inflammatory factors (interleukin (IL)-6, IL-8 and monocyte chemoattractant protein (MCP)-1) and structural and enzyme proteins associated with VSMC phenotypic transformation (smooth muscle actin alpha 2 (ACTA2), myosin heavy chain 11 (MYH11) and NADPH oxidase 4 (NOX4)).
Results:
Medin exposure increased VSMC gene expression and protein secretion of IL-6, IL-8 and MCP-1 (protein secretion 46.0±12.8x, 20.2±4.1x and 8.7±3.1x, respectively, medin 5 µM versus vehicle, all p<0.05). There was no change in gene or protein expressions of ACTA2, MYH11 and NOX4. Co-treatment with RO106-9920 reduced medin-induced increases in IL-6 and IL-8 and a trend towards reduced MCP-1 secretion.
Conclusions:
Medin induced pro-inflammatory activation of human brain VSMCs that is mediated, at least in part, by NFκB. Acute medin treatment did not alter structural proteins involved in VSMC phenotypic transformation. The findings support medin as a potential novel mediator of and therapeutic target for vascular aging pathology.
Insights
Medin protein accumulation in blood vessels promotes inflammation in human brain vascular smooth muscle cells, partly via the NFκB pathway. This suggests medin as a potential therapeutic target for vascular aging.
Area of Science:
- Vascular Biology
- Neuroscience
- Aging Research
Background:
- Medin, an amyloidogenic protein, accumulates in vasculature with aging.
- Vascular medin is linked to Alzheimer's disease, vascular dementia, and aortic aneurysms.
- Medin impairs vasodilation in human brain arteries, but its role in VSMC activation is unknown.
Purpose of the Study:
- To investigate the effects of medin on human brain vascular smooth muscle cell (VSMC) activation.
- To determine if medin influences pro-inflammatory factor expression in VSMCs.
- To assess medin's impact on VSMC structural proteins.
Main Methods:
- Human brain VSMCs were exposed to varying doses of medin.
- Gene and protein expression of pro-inflammatory factors (IL-6, IL-8, MCP-1) were quantified.
- Expression of VSMC structural proteins (ACTA2, MYH11, NOX4) was analyzed, with and without an NFκB inhibitor.
Main Results:
- Medin significantly increased VSMC gene and protein secretion of IL-6, IL-8, and MCP-1.
- No changes were observed in ACTA2, MYH11, or NOX4 gene or protein expression.
- NFκB inhibition partially reduced medin-induced pro-inflammatory factor secretion.
Conclusions:
- Medin induces pro-inflammatory activation in human brain VSMCs, mediated partly by NFκB.
- Medin does not acutely alter key structural proteins in VSMC phenotypic transformation.
- Medin represents a potential therapeutic target for vascular aging pathologies.
