Inflammation Journal doi: 10.3390/inflammj1010003

Authors: Ian M. Anderson Kristina C. MacLeod Camden Holm Solomon A. Mensah

This review examines how structural injury to the endothelial glycocalyx is known to initiate the collapse of caveolin-1-dependent caveolae, and how this may influence the dysregulation of endothelin type B receptors. The glycocalyx, caveolae, and endothelin type B receptors are proposed to form an integrated mechanosensory axis that coordinates shear-dependent signaling, redox control, and endothelin peptide clearance. Under physiological flow conditions, heparan sulfate-mediated mechanotransduction is known to sustain caveolin-1 expression, which preserves caveolar organization, endothelial nitric oxide synthase coupling, and localization of endothelin type B receptors. Under disturbed flow or inflammatory stress, enzymatic shedding of the glycocalyx is associated with reduced caveolin-1 stability and subsequent disruption of caveolar microdomains. These structural alterations coincide with the uncoupling of endothelial nitric oxide synthase, increased reactive oxygen species generation, enhanced endothelin-1 transcription, and possibly the impaired localization of the endothelin type B receptors meant to clear endothelin-1 peptides. The combination of these processes suggests a potentially self-amplifying interaction between mechanotransductive failure, increased oxidative stress, and endothelin imbalance. The objective here is to reframe the current understanding of glycocalyx degradation and caveolar collapse as direct upstream contributors to endothelin type B receptor dysfunction, while simultaneously highlighting the preservation of this pathway as a potential therapeutic focus in vascular diseases such as hypertension and atherosclerosis. A stronger mechanistic definition of the relationship between glycocalyx degradation, caveolae destabilization, and altered endothelin type B receptor function is necessary to clarify how vascular injury may lead to persistent endothelial dysfunction. Future research in this area may present opportunities for therapeutic interventions focused on preservation or restoration of glycocalyx integrity and function and may allow interruption of the proposed pathological feedback loop responsible for these diseases, improving patient outcomes.

Inflammation Journal doi: 10.3390/inflammj1010002

Authors: Mohammad Movahedi Angela Cesta Sibel Zehra Aydin Pooneh Akhavan Tetyana Kendzerska Claire Bombardier Bindee Kuriya

Background: Rheumatoid arthritis (RA) is linked to increased risks of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), malignancy, and mortality. However, differences in these risks by treatment class—particularly among older adults with cardiovascular (CVD) risk factors—remain unclear. Methods: We conducted a population-based cohort study using Ontario administrative data. Patients aged ≥67 years with incident RA (2008–2013) were followed through 2023. Outcomes included healthcare utilization for MACE and VTE, all-cause mortality, and cancer-related encounters. Time-varying treatment groups were: no csDMARD/advanced therapy (AT), glucocorticoids (GC) only, csDMARDs (reference), and biologic/targeted synthetic DMARDs (b/tsDMARDs). Weighted Fine–Gray models within a marginal structural framework were used, stratified by baseline CVD risk. Results: Among 10,058 patients, 80% had high CVD risk. Compared with csDMARDs, untreated patients (SHR 15.0; 95% CI 13.8–16.2) and GC users (SHR 1.29; 95% CI 1.13–1.47) had higher MACE risk, while AT use was associated with lower risk (SHR 0.53; 95% CI 0.37–0.77). Similar patterns were observed in low-risk patients. AT use was not associated with VTE. Untreated and GC users had increased mortality, whereas AT use reduced mortality. Increased cancer-related utilization was observed only in untreated patients. Conclusion: Treatment type strongly influences major outcomes in older adults with RA, underscoring the importance of integrating CVD and thrombotic risk into therapeutic decisions.

Inflammation Journal doi: 10.3390/inflammj1010001

Authors: Juan Pablo de Rivero Vaccari

Vast advances have taken place since the first century AD, when Roman scholar Aulus Cornelius Celsus described “Rubor, et tumor, cum calore et dolore” (redness and swelling with heat and pain) in his ‘De Medicina’ [...]