ArticleCirculation research2025
Paracrine Smooth Muscle-to-Endothelial Signaling via TNF Elevates Blood Pressure in Obesity.
Article in Circulation research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed.
- VSMCs and the immune microenvironment: a multidimensional regulatory network driving vascular injury and repair.Frontiers in immunology · 2026Review
- Smooth Muscle LRRC8A Knockout Preserves Vascular Function in Ang II Hypertension.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Experimental Models for Studying Cardiovascular Dysfunction in Metabolic Syndrome.Handbook of experimental pharmacology · 2026Review
- Smooth Muscle-Induced Endothelial Dysfunction in Obesity; Don't Just Blame the Middleman.Circulation research · 2025Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
13 authors.
Funding
Abstract
backgroundLoss of endothelial function is a key contributor to obesity-induced hypertension. Obesity can cause chronic, low-grade inflammation, leading to abnormal blood vessel function. The release of inflammatory cytokines is commonly attributed to immune cells, but recent studies suggest that vascular cells can also release these cytokines. We tested the hypothesis that vascular wall-derived inflammatory cytokines act locally to impair endothelial function and elevate blood pressure in obesity.
methodsThe levels of inflammatory cytokines were analyzed in endothelial cells (ECs) and smooth muscle cells (SMCs) from small arteries of high-fat diet-fed mice and individuals with obesity. We utilized inducible, EC- or SMC-specific deletion and receptor inhibition studies to determine whether inflammatory signaling between SMCs and ECs can be targeted to improve endothelial function and lower blood pressure in obesity.
resultsTNF (tumor necrosis factor) was selectively upregulated in SMCs from small arteries of obese mice and human subjects with obesity. TNF colocalized with TNFRI (TNF receptor I) at endothelial projections to SMCs or myoendothelial projections in obesity. SMC-specific deletion of TNF or EC-specific deletion of TNFRI improved endothelial function and lowered blood pressure in obese mice. Notably, deleting TNF from ECs or TNFRI from SMCs had no impact on endothelial function or blood pressure in obesity. Furthermore, the deletion of TNF from SMCs or TNFRI from ECs decreased the levels of inducible nitric oxide (NO) synthase and peroxynitrite, leading to enhanced activity of TRPV4 (transient receptor potential vanilloid 4) ion channels and improved endothelial function. In addition, specific inhibition of TNFRI also rescued endothelial function and lowered blood pressure in obesity.
conclusionsOverall, these findings show that paracrine signaling from SMCs to ECs via TNF elevates blood pressure in obesity. Consequently, targeting smooth muscle TNF or endothelial TNFRI offers a potential approach for lowering blood pressure in obesity.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.