Biology subjects

Matz, J.

Publications and source records attributed to Matz, J..

5 recordsLinked to original sources

bioRxiv2026

Structural Lung Remodeling Precedes Functional Decline After Chronic Smoldering Douglas Fir Smoke Exposure in Apoe-/- Mice

Wildland firefighters experience repeated exposure to wildfire smoke, yet the pathophysiological mechanisms underlying chronic inhalation injury remain poorly understood. Although prior studies report parenchymal destruction following prolonged woodsmoke exposure, the temporal relationship between molecular, structural, and functional decline following inhalation of smoke from needles/leaves remains unclear. To address this gap, we characterized coordinated changes in lung structure, function, and underlying molecular disruptions using a dosimetry-based murine model approximating 7-14 years of firefighter service. Male apolipoprotein E-deficient mice were exposed to smoldering Douglas fir needle smoke (40 mg/m3, 2 h/day, 5 days/week) for 8 or 16 weeks. Immunofluorescence analyses revealed an early elastolytic response at 8 weeks, with increased neutrophil elastases and matrix metalloproteinases-9 and -12, accompanied by elevated surfactant protein-D, compared to air controls. These changes were resolved by 16 weeks despite progressive tissue injury. Airspace enlargement was evident at 8 weeks, progressed by 16 weeks, and included increased alveolar blunting and septal wall thickening at the later time point. Cleaved caspase-3 was elevated at 16 weeks, indicative of advanced parenchymal damage and apoptosis. Epithelial tight-junction protein ZO-1 intensity was reduced at both evaluation points, whereas the epithelial-to-mesenchymal marker N-cadherin remained undetectable in the alveolar epithelium. Functional impairment as evident by increased static compliance and upward shifts in pressure-volume curves was only significant after 16 weeks of exposure. Findings indicate that molecular and structural injury of tissue destruction preceded measurable functional decline, underscoring the need for early biomarkers to identify smoke-induced lung injury in wildland firefighters before function loss occurs.

physiology↗

bioRxiv2026

Occupationally Relevant Wildfire Smoke Inhalation Impairs Nitric Oxide Signaling and Promotes Progressive Aortic Stiffening in Hypercholesterolemic Mice

BackgroundWildland firefighters experience repeated occupational exposure to wildfire smoke at high particulate matter (PM) concentrations, leading to elevated cardiovascular disease risk and hypertension prevalence. However, the pathophysiological processes linking cumulative smoke inhalation to vascular damage and blood pressure elevation remain poorly characterized. To evaluate these effects under controlled exposure conditions, we used a preclinical exposure model calibrated to match the cumulative PM burden deposited in wildland firefighter airways over 7-14 years of service. Male apolipoprotein E knockout (Apoe-/-) mice underwent whole-body inhalation of Douglas fir smoke or filtered air for 2 hours/day, 5 days/week, for 8 or 16 weeks at target PM concentrations of 40 mg/m3. ResultsProlonged smoke exposure induced sustained elevation of circulating tumor necrosis factor-alpha (TNF-), interleukin-1 beta (IL-1{beta}), and interleukin-6 (IL-6), coupled with diffused nuclear factor kappa B (NF-{kappa}B) activation throughout the aortic wall. Smoke inhalation disrupted endothelial adherens junctions, upregulated intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and promoted monocyte recruitment to aortic tissues, concurrent with enhanced monocyte chemoattractant protein-1 (MCP-1) expression. Oxidative stress was evidenced by increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit 2 (NOX2) expression, elevated superoxide levels, and endothelial nitric oxide synthase (eNOS) uncoupling in the aorta, leading to lipid peroxidation and accompanied by intimal apoptosis. These inflammatory and oxidative perturbations occurred alongside a pro-fibrotic phenotypic shift characterized by transforming growth factor beta 1 (TGF-{beta}1) upregulation, myofibroblast differentiation, and progressive collagen accumulation in medial and adventitial compartments of the aortic wall. Functionally, smoke exposure progressively impaired aortic cyclic distensibility through combined wall thickening and circumferential tissue stiffening, while severely attenuating endothelium-dependent and nitric oxide (NO)-mediated vasodilation. These functional and structural shifts culminated in elevated systolic and diastolic blood pressures. While endothelial dysfunction reached maximal impairment by 8 weeks, aortic stiffening continued to worsen through 16 weeks of exposure, demonstrating differential temporal progression of vascular damage. ConclusionsThese findings demonstrate that occupationally relevant wildfire smoke exposure produces convergent inflammatory, oxidative, and profibrotic vascular remodeling with progressive loss of arterial compliance and impaired endothelium-dependent vasodilation, underscoring potential vascular targets for cardiovascular health surveillance and risk mitigation in wildland firefighters.

pharmacology and toxicology↗

bioRxiv2026

Smooth muscle cell estrogen receptor alpha promotes arterial stiffness in the absence of estradiol

BackgroundClinical evidence supports a greater impact of arterial stiffening in cardiovascular mortality in women versus men. Arterial stiffness increases across the menopausal transition, implicating a role of the loss of estrogens in arterial stiffening, but mediating mechanisms remain unclear. MethodsThe role of estradiol and smooth muscle cell (SMC) estrogen receptor alpha (ER) in arterial stiffening, by aortic pulse wave velocity (PWV), was assessed in 3 models: (1) the loss of estradiol in young, female mice comparing sham surgery or bilateral ovariectomy (OVEX) {+/-} estradiol, (2) the impact of sham versus OVEX surgery in young, female SMC-ER-intact and SMC-ER-knockout (KO) littermates, and (3) arterial stiffening during natural aging by comparing young and aged, female and male SMC-ER-intact and SMC-ER-KO littermates. Mechanistic pathways were assessed using histological assessment of aortic fibrosis and elastin degradation, aortic MMP expression, and atomic force microscopy. ResultsOVEX increased PWV and aortic medial fibrosis, with no impact on elastin integrity, in young female mice. Arterial stiffening and fibrosis were prevented in OVEX mice that were supplemented with estradiol. OVEX-induced arterial stiffening in SMC-ER-intact female mice was prevented in SMC-ER-KO littermates. In this model, OVEX was also associated with increased aortic medial fibrosis without changes in elastin integrity. Aging from 3 to 18 months significantly increased PWV in female and male SMC-ER-intact mice. Aging-induced stiffening was fully prevented in female and partially prevented in male SMC-ER-KO mice. SMC-ER contributes to aging-associated arterial stiffening by sex-specific mechanisms, including elastin degradation in females and phenotypic changes in SMC stiffness and probability to form cellular adhesions in males. Circulating estradiol was significantly decreased in serum from aged compared with young female mice. ConclusionsThese findings support that SMC-ER contributes to arterial stiffening in female and male mice in situations where the vasculature is exposed to low levels of estradiol.

physiology↗

bioRxiv2024

Chronic Pod-Mod E-Cigarette Aerosol Exposure Induces Aortic Dysfunction in Hypercholesterolemic Mice: Role of Oxidative Stress and Inflammation

ObjectiveElectronic (e-)cigarettes are the most used tobacco product amongst youth, and adult smokers favor e-cigarettes over approved cessations aids. Despite the lower perceived harm of vaping compared to smoking, inhalation of e-cigarette aerosol elicits cardiovascular responses that may lead to permanent injury when repeated over time. We thus aimed to infer the long-term outcomes of vaping on the function and structure of the aorta and shed light on the underlying cellular and molecular mechanisms. Approach and ResultsWe exposed female hypercholesterolemic mice to either pod-mod e-cigarette aerosol or room air daily for 24 weeks. Chronic inhalation of e-cigarette aerosol triggered accumulation of inflam-matory signals systemically and within aortic tissues, as well as T lymphocyte accrual in the aortic wall. Reduced eNOS expression and enhanced ROS production following eNOS uncoupling and NADPH oxi-dase activation curbed nitric oxide availability in the aorta of mice exposed to e-cigarette aerosol, impairing the endothelium-dependent vasodilatation that regulates blood flow distribution. Inhalation of e-cigarette aerosol thickened and stiffened aortic tissues via collagen deposition and remodeling, hindering the storage of elastic energy and limiting the cyclic distensibility that enables the aorta to function as a pressure reservoir. These effects combined contributed to raising systolic and pulse pressure above control levels. ConclusionsChronic inhalation of aerosol from pod-mod e-cigarettes promotes oxidative stress, inflammation, and fibrosis within aortic tissues, significantly impairing passive and vasoactive aortic functions. This evidence provides new insights on the biological processes that increase the risk for adverse cardio-vascular events as a result of pod-mod e-cigarette vaping.

bioengineering↗

bioRxiv2022

Mapping the unicellular transcriptome of the ascending thoracic aorta to changes in mechanosensing and mechanoadaptation during aging

Aortic stiffening is an inevitable manifestation of chronological aging, yet the mechano-molecular programs that orchestrate region- and layer-specific adaptations along the length and through the wall of the aorta are incompletely defined. Here, we show that the decline in passive cyclic distensibility is more pronounced in the ascending thoracic (ATA) compared to distal segments of the aorta and that tissues in both the medial and adventitial compartments of the ATA stiffen during aging. Single-cell RNA sequencing of aged ATA tissues reveals altered cellular senescence, remodeling, and inflammatory responses accompanied by enrichment of T-lymphocytes and rarefaction of vascular smooth muscle cells, compared to young samples. T-lymphocytes accumulate in the adventitia and likely promote fibrosis, while activation of mechanosensitive piezo-1 enhances medial vasoconstriction. These results portray the immuno-mechanical aging of the ATA as a process that culminates in a stiffer conduit permissive to the accrual of multi-gerogenic signals priming to disease development.

bioengineering↗