Biology subjects

Figueiredo, V.

Publications and source records attributed to Figueiredo, V..

3 recordsLinked to original sources

bioRxiv2025

Caspase-Driven Microvascular Inflammation and Hypoperfusion in Intravascular Hemolysis: Roles of Leukocyte and Endothelial Activation

Intravascular hemolysis (IVH), a pathological process associated with various conditions, triggers vascular responses; however, the molecular and cellular mechanisms driving this process remain unclear. To explore the role of NLRP3 inflammasome- and caspase-dependent pathways in IVH-induced inflammation, we used in vivo models of acute and chronic IVH, alongside hemestimulation of endothelial cells, thereby isolating this disease mechanism from its etiological causes. Acute IVH induced immediate inflammatory responses in C57BL/6 mice, marked by the release of pro-inflammatory molecules, including IL-1{beta}, within just 15 minutes and NLRP3-dependent caspase activation in circulating leukocytes. Chronic IVH processes in mice elevated liver monocyte-derived macrophage caspase activity and NLRP3 protein expression. In turn, acute IVH impaired cutaneous microvascular blood flow and perfusion, and induced microvascular leukocyte recruitment, which were both caspase-1-dependent. Acute IVH induced time-dependent CD11b-integrin-subunit presentation on leukocytes, while heme stimulation augmented endothelial cell adhesion molecule expression, potentially promoting leukocyte recruitment. This endothelial activation was associated with reactive oxygen species generation, which promoted caspase-1 activation and was key to adhesion molecule upregulation. Our findings highlight a role for inflammasome-/caspase-dependent pathways in hemolytic inflammation, contributing to microvascular leukocyte recruitment and particularly to cutaneous hypoperfusion, a consequence that could facilitate the progression of skin lesions. Targeting caspase-dependent pathways and their downstream effects in disorders that display IVH may offer therapeutic potential for maintaining endothelial integrity, reducing leukocyte activation, and mitigating ischemic injury. NEW & NOTEWORTHYThis study identifies caspase-1 as a driver of the vascular inflammation and hypoperfusion induced by intravascular hemolysis (IVH). Using in vivo models and heme-stimulated endothelial cells, we show that hemolysis rapidly induces caspase-1-dependent endothelial-leukocyte recruitment, microvascular dysfunction, and also IL-1{beta} release. Oxidative stress promotes heme-induced endothelial caspase-1 activation and adhesion molecule expression, potentially amplifying vascular dysfunction. These findings provide insight into IVH-driven pathology in hemolytic disorders, including sickle cell disease.

physiology↗

bioRxiv2021

Modulation of early level EEG signatures by distributed facial emotion cues

Face perception plays an important role in our daily social interactions, as it is essential to recognize emotions. The N170 Event Related Potential (ERP) component has been widely identified as a major face-sensitive neuronal marker. However, despite extensive investigations conducted to examine this electroencephalographic pattern, there is yet no agreement regarding its sensitivity to the content of facial expressions. Here, we aim to clarify the EEG signatures of the recognition of facial expressions by investigating ERP components that we hypothesize to be associated with this cognitive process. We asked the question whether the recognition of facial expressions is encoded by the N170 as weel as at the level of P100 and P250. In order to test this hypothesis, we analysed differences in amplitudes and latencies for the three ERPs, in a sample of 20 participants. A visual paradigm requiring explicit recognition of happy, sad and neutral faces was used. The facial cues were explicitly controlled to vary only regarding mouth and eye components. We found that non neutral emotion expressions elicit a response difference in the amplitude of N170 and P250. In contrast with the P100, there by excluding a role for low level factors. Our study brings new light to the controversy whether emotional face expressions modulate early visual response components, which have been often analysed apart. The results support the tenet that neutral and emotional faces evoke distinct N170 patterns, but go further by revealing that this is also true for P250, unlike the P100.

neuroscience↗

bioRxiv2019

Depletion of resident muscle stem cells inhibits muscle fiber hypertrophy induced by lifelong physical activity

BackgroundA reduction in skeletal muscle stem cell (satellite cell) content with advancing age is thought to directly contribute to the progressive loss of skeletal muscle mass and function with aging (sarcopenia). However, we reported that the depletion of satellite cells throughout adulthood did not affect the onset or degree of sarcopenia observed in sedentary old mice. The current study was designed to determine if lifelong physical activity would alter the requirements for satellite cells during aging.\n\nMethodsWe administered vehicle or tamoxifen to adult (5 months old) female Pax7-DTA mice for 5 consecutive days to effectively deplete satellite cells. Following a 2-month washout period, mice were assigned to physically active (free access to a running wheel) or sedentary (locked running wheel) conditions. Thirteen months later, at a mean age of 20 months, mice were sacrificed for subsequent analysis.\n\nResultsSatellite cell depletion throughout adulthood negatively impacted physical function and limited muscle fiber hypertrophy in response to lifelong physical activity. To further interrogate these findings, we performed transcriptome-wide analyses on the hind limb muscles that experienced hypertrophic growth (plantaris and soleus) in response to lifelong physical activity. Our findings demonstrate that satellite cell function is muscle type-specific; fusion with fibers is apparent in oxidative muscles, while initiation of Gi2 signaling appears to require satellite cells in glycolytic muscles to induce muscle growth..\n\nConclusionsThese findings suggest that satellite cells, or their secretory products, are viable therapeutic targets to preserve physical function with aging and promote muscle growth in older adults who regularly engage in physical activity.

physiology↗