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

ObjectivesAging 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.MethodsFormalin-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.ResultsThe 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.ConclusionsScanning 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.

Blood vessels and the endothelium

The blood vessel wall consists of three layers: the intima, media, and adventitia. Not all vessels have each layer, and the layers vary in size and structure between vessels. The intima is made up of a single layer of endothelial cells on a basement membrane, beneath which—depending on vessel size—there may be a layer of fibroelastic connective tissue and an internal elastic lamina that provides both structure and flexibility. Embedded in the intima are pericytes. The media is made up of smooth muscle cells, elastic laminae, and extracellular matrix. The adventitia is the outermost part of the vessel, composed mainly of fibroelastic tissue but also containing nerves, small feeding blood vessels (the vasa vasorum), and lymph vessels. The adventitia is directly related to the surrounding perivascular adipose tissue.

Modeling Prestress-Driven Buckling Behavior of Elastic Lamina in the Aortic Media

Mathematical modeling of the thoracic aorta is important for understanding the development and progression of various cardiovascular diseases, helping to detect extraordinary stress distributions of the hypertensive aortic wall, even in early stages. However, it is difficult to ensure the biofidelity of biological materials in formulating a mathematical model. In a freshly isolated aortic media, composed mainly of smooth muscle cell layers (SMLs) and elastic laminae (ELs), circumferential EL waviness and longitudinal EL undulation are often observed because of the structural “buckling” of ELs. This is considered to be closely associated with residual stresses of SMLs and ELs in the aortic wall but the mechanism underlying such EL buckling behavior remains unclear. In the present study, a series of numerical simulations were designed to identify effective mechanical parameters to reproduce EL buckling in the aortic media. We found that prestress initially administered to ELs in the circumferential and axial directions, and the predefined internodal distance, which couples the SML and EL, are essential to computationally reconstruct the circumferential EL waviness and the longitudinal EL undulation in an unloaded state. We also proposed a set of equations based on the numerical results and successfully predicted EL buckling behaviors of the aorta in vitro.

Oxidative Stress in the Developing Rat Brain due to Production of Reactive Oxygen and Nitrogen Species

Oxidative stress after birth led us to localize reactive oxygen and nitrogen species (RONS) production in the developing rat brain. Brains were assessed a day prenatally and on postnatal days 1, 2, 4, 8, 14, 30, and 60. Oxidation of dihydroethidium detected superoxide; 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate revealed hydrogen peroxide; immunohistochemical proof of nitrotyrosine and carboxyethyllysine detected peroxynitrite formation and lipid peroxidation, respectively. Blue autofluorescence detected protein oxidation. The foetuses showed moderate RONS production, which changed cyclically during further development. The periods and sites of peak production of individual RONS differed, suggesting independent generation. On day 1, neuronal/glial RONS production decreased indicating that increased oxygen concentration after birth did not cause oxidative stress. Dramatic changes in the amount and the sites of RONS production occurred on day 4. Nitrotyrosine detection reached its maximum. Day 14 represented other vast alterations in RONS generation. Superoxide production in arachnoidal membrane reached its peak. From this day on, the internal elastic laminae of blood vessels revealed the blue autofluorescence. The adult animals produced moderate levels of superoxide; all other markers reached their minimum. There was a strong correlation between detection of nitrotyrosine and carboxyethyllysine probably caused by lipid peroxidation initiated with RONS.

Computational modelling suggests good, bad and ugly roles of glycosaminoglycans in arterial wall mechanics and mechanobiology

The medial layer of large arteries contains aggregates of the glycosaminoglycan hyaluronan and the proteoglycan versican. It is increasingly thought that these aggregates play important mechanical and mechanobiological roles despite constituting only a small fraction of the normal arterial wall. In this paper, we offer a new hypothesis that normal aggregates of hyaluronan and versican pressurize the intralamellar spaces, and thereby put into tension the radial elastic fibres that connect the smooth muscle cells to the elastic laminae, which would facilitate mechanosensing. This hypothesis is supported by novel computational simulations using two complementary models, a mechanistically based finite-element mixture model and a phenomenologically motivated continuum hyperelastic model. That is, the simulations suggest that normal aggregates of glycosaminoglycans/proteoglycans within the arterial media may play equally important roles in supporting (i.e. a structural role) and sensing (i.e. an instructional role) mechanical loads. Additional simulations suggest further, however, that abnormal increases in these aggregates, either distributed or localized, may over-pressurize the intralamellar units. We submit that these situations could lead to compromised mechanosensing, anoikis and/or reduced structural integrity, each of which represent fundamental aspects of arterial pathologies seen, for example, in hypertension, ageing and thoracic aortic aneurysms and dissections.