Evaluation of the presence of TRPC6 channels in human vessels: A pilot study using immunohistochemistry
Jan Abdinghoff1, Davide Servello1, Tobias Jacobs1
1Institute of Anatomy and Cell Biology, Saarland University, Medical Campus, D-66424 Homburg/Saar, Germany.
Insights
Transient Receptor Potential Canonical 6 (TRPC6) channels are crucial for vascular health. This study found TRPC6 expression predominantly in human vessel intima and adventitia, not the tunica media, challenging previous assumptions.
Area of Science:
- Vascular Biology
- Ion Channel Physiology
- Human Histopathology
Background:
- Transient Receptor Potential Canonical 6 (TRPC6) channels are calcium-permeable ion channels.
- TRPC6 plays roles in vascular physiology (e.g., Bayliss effect) and pathophysiology (e.g., hypertension, atherosclerosis).
- Previous understanding of TRPC6 localization in human vessels was limited, often extrapolated from animal models.
Purpose of the Study:
- To systematically investigate the presence and localization of TRPC6 channels in human vessels.
- To provide histological evidence of TRPC6 expression in different vascular layers.
- To reconcile findings with existing knowledge from animal studies.
Main Methods:
- Analysis of 40 human vessel sections from nine body donors.
- Immunohistochemistry and Western blotting using a validated anti-TRPC6 antibody.
- Microscopic examination and protein detection to identify TRPC6 expression patterns.
Main Results:
- TRPC6 channel expression was detected in the intima and adventitia of over half of the analyzed human vessel samples.
- Expression of TRPC6 in the tunica media was rare, observed in only one out of 40 cases.
- Findings confirm TRPC6's role in the human vasculature, particularly in the intima.
Conclusions:
- TRPC6 channels are present in human vessel intima and adventitia, supporting their physiological and pathophysiological roles.
- The limited expression in the tunica media contrasts with assumptions based on animal studies.
- This study provides crucial histological data on TRPC6 localization in human vasculature.
Abstract:
The TRPC6 channel is permeable to calcium ions as well as other ions and plays an important role in the physiology and pathophysiology of vessels. Findings from animal and cell culture experiments have shown its involvement in important vascular processes such as the Bayliss effect or endothelial-mediated vasodilatation. Furthermore, the relevance of TRPC6 channels in humans has become apparent based on diseases such as idiopathic pulmonary arterial hypertension, focal segmental glomerulosclerosis and atherosclerosis, amongst others. However, histological evidence that systematically detects TRPC6 channels in human vessels has not been provided to date. In this study, 40 vessel sections from nine body donors were obtained, processed and stained with a knockout-validated antibody against the TRPC6 protein using immunohistochemistry and western blotting. More than half of the samples yielded evidence of TRPC6 channel expression in the intima and adventitia. TRPC6 channels were detected in the tunica media in only one of 40 cases. TRPC6 detection in the human intima confirmed several demonstrated physiological aspects of the TRPC6 channels in the vasculature and may also be involved in associated human diseases. The near absence of TRPC6 channels in the tunica media was in contrast to a view that is primarily based on animal studies, from which its presence was assumed.
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