bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2020.06.03.131631

Tunica intima compensation for reduced stiffness of the tunica media in aging renal arteries as measured with scanning acoustic microscopy

Miura, k.
View original source ↗Export metadata ↓

Abstract

Objectives Aging causes stiffness and decreased function of the renal artery (RA). Histological study with light microscopy can reveal microscopic structural remodeling but no functional changes. The present study aimed to clarify the association between structural and functional aging of the RA through the use of scanning acoustic microscopy.Methods Formalin-fixed, paraffin-embedded cross-sections of renal arteries from 64 autopsy cases were examined. Speed-of-sound (SOS) values of three layers, which correspond to the stiffness, were compared among different age groups. SOS of the tunica media was examined in terms of blood pressure (BP) and SOS of the ascending aorta. Vulnerability to proteases was assessed by SOS reduction after collagenase treatment.Results The tunica intima presented inward hypertrophy with luminal narrowing, and the tunica media showed outward hypertrophic remodeling with aging. SOS of the tunica media and internal and external elastic laminae showed a reverse correlation with age. SOS of the tunica media was negatively correlated with BP and strongly associated with that of the aorta. The tunica media of young RAs were more sensitive to collagenase compared with the old ones.Conclusions Scanning acoustic microscopy is useful for observing the aging process of the RA. This technique simultaneously shows structural and mechanical information from each portion of the RA. In the process of aging, the RA loses contractile function and elasticity as a result of protease digestion. The tunica media and the internal and external elastic laminae exhibit reduced stiffness, but the tunica intima stiffens with atherosclerosis. As a consequence, the RA’s outer shape changes from round to oval with inward and outward hypertrophy. This indicates that the inner resistant intima supports the mechanical weakness of the tunica media to compensate for an increase in BP with aging.View Full Text

Source connections

Explore related subjects

pathologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Miura, k.. 2020-06-03. Tunica intima compensation for reduced stiffness of the tunica media in aging renal arteries as measured with scanning acoustic microscopy. https://doi.org/10.1101/2020.06.03.131631

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

sPLA2 inhibitor-loaded nanoparticles mitigate spontaneous osteoarthritis in guinea pigs

Osteoarthritis (OA) is a prevalent degenerative joint disease lacking effective disease-modifying therapies. Secreted phospholipase A2 (sPLA2), a key upstream regulator of inflammatory lipid mediators, has been implicated in OA pathogenesis, but its therapeutic potential in age-related OA remains unclear. Here, we evaluated the role of sPLA2 and the efficacy of nanoparticle-mediated sPLA2 inhibition in a spontaneous OA model using female Dunkin-Hartley (DH) guinea pigs. We first characterized OA progression and observed age-dependent increases in cartilage degeneration, synovitis, oxidative stress, and sPLA2 expression and enzymatic activity. We then developed sPLA2 inhibitor (thioetheramide-PC)-loaded nanoparticles (sPLA2i-NPs) and demonstrated their superior ability, compared to free inhibitor, to prevent IL-1{beta}-induced cartilage degeneration in guinea pig cartilage explants. In vivo, intra-articular administration of sPLA2i-NPs from 3 months of age significantly attenuated cartilage destruction, synovial inflammation, and osteophyte formation in 7- and 10-month-old guinea pigs. These structural improvements were accompanied by normalization of anabolic and catabolic gene expression and a marked reduction in synovial fluid sPLA2 activity. Importantly, longitudinal gait analysis revealed that sPLA2i-NP treatment preserved limb loading, propulsion, and locomotor performance, demonstrating functional recovery. No systemic toxicity was observed following long-term treatment. Collectively, our findings identify sPLA2 as a key driver of spontaneous OA and establish nanoparticle-mediated sPLA2 inhibition as a promising disease-modifying strategy for age-related OA.

pathology↗
bioRxiv2026

Midlife nonlinearities across scale in Biondi body amyloid formation in the human choroid plexus

Human choroid plexus epithelial cells (CPECs), which produce cerebrospinal fluid and form the blood-cerebrospinal fluid barrier, accumulate discrete intracellular amyloid inclusions called Biondi bodies (BBs). Using systematic manual and machine learning approaches on the choroid plexus glomus, we determined the percentages of CPECs containing thioflavin S-stained BBs as well as BB load and spatial distributions in whole slide images from 77 cases across the human lifespan. On average, BB prevalence was near zero until age 40, rose steeply in the 5th and 6th decades, and exceeded 50% after age 70. As prevalence plateaued, BB load continued to rise with age. Accelerated BB accumulation was seen in two cases of diabetic ketoacidosis, including a 16-year-old, while an 85-year-old with the relatively rare APOE2/E2 genotype had fewer BBs than expected. BB prevalence in the choroid plexus glomus was not associated with Alzheimer's disease, but was lower in females than males. Notably, spatial clustering of BBs was universal across cases while nearest-neighbor analyses suggested cell-to-cell, prion-like BB spread that can account for the nonlinearities seen at tissue and population scales. The abrupt, nonlinear BB accumulation during midlife coincides with or precedes other common aging-associated neuropathologies of the human brain, consistent with broad BB and choroid plexus contributions to brain aging and disease.

pathology↗
bioRxiv2026

Elevated precontractile calcium set point is sustained by limited PMCA1 export in dystrophic muscle

Duchenne muscular dystrophy is caused by loss of dystrophin and marked by elevated muscle calcium, usually attributed to contraction-induced membrane damage. Whether calcium rises before muscle can contract, and what sustains it, is unresolved. In Caenorhabditis elegans embryos and patient-derived human myoblasts, dystrophic muscle carries an elevated resting calcium set point before contraction is possible. Embryonic calcium is elevated 400 minutes after fertilization, before movement is detectable or the neuromuscular junction forms. Silencing the plasma membrane calcium pump gene mca-1 raises calcium in wild-type but not dystrophic animals, whereas silencing its paralogue raises it in both: the limitation is specific to that export route. Dystrophic human myoblasts have less pump; pump inhibition or silencing increases calcium preferentially in healthy cells, and raising pump expression lowers calcium most in dystrophic cells. Constrained calcium export is an early, continuing determinant of the dystrophic set point.

pathology↗