Biology subjects

Martin-Ventura, J. L.

Publications and source records attributed to Martin-Ventura, J. L..

3 recordsLinked to original sources

bioRxiv2025

Integrative multi-layer workflow for quantitative analysis of post-translational modifications

Novel algorithms based on ultratolerant database searching have paved the way for comprehensive analysis of all possible post-translational modifications (PTM) that can be detected by mass spectrometry-based proteomics, obviating their prior knowledge. These tools together with novel quantitative statistical models allow hypothesis-free approaches to study the role and impact of PTM on biological systems. However, interpretation of this information from a pathophysiological perspective is challenging due to the huge amounts of PTM data, the existence of chemical, structural, and statistical artifacts and the lack of dedicated tools for their analysis. Here we propose a novel integrative workflow that automatically captures several layers of PTM-related information, including variations in trypsin efficiency, zonal changes, specific PTM changes and hypermodified regions, allowing advanced control of artefacts and coherent and comprehensive interpretation of PTM data. We show the performance of the new workflow by reanalyzing proteomics data from animal models of mitochondrial heteroplasmy and ischemia/reperfusion, revealing relevant PTM information not previously detectable, including consistent detection of novel oxidative modifications in Met and Cys residues from raw proteomics data. The workflow is available through the application PTM-compass.

bioinformatics↗

bioRxiv2024

Integrated Stress Response Triggered by Excessive Glycosylation Drives Thoracic Aortic aneurysm

Thoracic aortic aneurysms and dissections (TAAD) are marked by degenerative changes in the aortic media. Marfan syndrome is the most common inherited connective tissue disorder associated with TAAD. While vascular smooth muscle cell (VSMC) metabolism is emerging as a targetable driver of aortic aneurysm, surgical interventions remain the primary strategy to prevent aortic dissection. Our research indicates that the hexosamine biosynthetic pathway (HBP), a branch of glycolysis, is upregulated in aortas from the Fbn1C1041G/+ Marfan Syndrome mouse model. Enhancing HBP activity promotes aortic dilation and accumulation glycan-rich extracellular matrix, contributing to aortic medial degeneration in wild-type mice. Mechanistically, fueling HBP activity induces VSMC dysfunction through excessive glycosylation, which activates the Integrated Stress Response (ISR). Pharmacological inhibition of HBP, along with ISR inhibition, successfully reverses aortic dilation and aortic medial degeneration in Fbn1C1041G/+ Marfan Syndrome mouse model. Additionally, Marfan Syndrome patients show elevated levels of HBP metabolites in blood plasma and serum, and heightened HBP-ISR signaling in patients with TAAD. These findings unveil a potential causative role for the HBP-ISR axis in medial degeneration in human TAAD, underscoring the need for evaluating HBP and ISR pathway as novel biomarkers and therapeutic strategies for thoracic aortic aneurysm.

molecular biology↗

bioRxiv2021

MDA-LDL vaccination induces athero-protective germinal center-derived antibody responses

Atherosclerosis is a chronic inflammatory disease of the arteries that can lead to thrombosis, infarction and stroke and is the leading cause of mortality worldwide. Immunization of pro-atherogenic mice with malondialdehyde-modified low-density lipoprotein (MDA-LDL) neo-antigen is athero-protective. However, the immune response to MDA-LDL and the mechanisms responsible for this athero-protection are not completely understood. Here, we find that immunization of mice with MDA-LDL elicits memory B cells, plasma cells, and switched anti-MDA-LDL antibodies as well as clonal expansion and affinity maturation, indicating that MDA-LDL triggers a bona fide germinal center antibody response. Further, Prdm1fl/fl Aicda-Cre+/ki Ldlr-/- pro-atherogenic chimeras, which lack germinal center-derived plasma cells, show accelerated atherosclerosis. Finally, we show that MDA-LDL immunization is not athero-protective in mice lacking germinal-center derived plasma cells. Our findings give further support to the development of MDA-LDL-based vaccines for the prevention or treatment of atherosclerosis.

immunology↗