The topographic distribution of atherosclerotic lesions is influenced by biochemical factors intrinsic to the arterial wall. In the present work we have investigated whether the composition/chemical structure of glycosaminoglycans constitutes one of these factors. Normal human arteries were obtained at necropsy, and in order of decreasing susceptibility to atherosclerosis, consisted of the abdominal and thoracic aortas and the iliac and pulmonary arteries. The results showed similar concentrations of total glycosaminoglycan and collagen. Of the glycosaminoglycans known to interact with low-density lipoprotein (LDL), dermatan sulfate was present in all arteries in comparable concentrations, but the aortas had a 30% higher content of chondroitin 4/6-sulfate, which in turn was slightly enriched in 6-sulfated disaccharide units. LDLaffinity chromatography with dermatan sulfate+chondroitin 4/6-sulfate fractions demonstrated that increasing affinity to LDL matched an increasing susceptibility to atherosclerosis. Analysis of glycosaminoglycans in the eluates indicated a positive correlation between affinity to LDL and increasing molecular weight and the existence of a fraction of glycosaminoglycans of high affinity to LDL in the aortas only. These results suggest that arterial glycosaminoglycans participate in the multifactorial mechanisms that modulate the differential localization of atherosclerotic lesions. 1 However, factors intrinsic to the arterial bed and its bloodcarrying functions also influence the occurrence of lesions. The primary evidence came from morphological study of necropsy material, which demonstrated that the incidence and/or severity of atherosclerotic lesions differed as a function of anatomic location.2 -3 Additionally, these studies revealed that in affected arteries, lesions tended to be located at critical sites, such as the entrances of vessels and flow dividers, where the effects of fluid turbulence would be more pronounced. Experimental physiological investigations have supported these findings 68 and have shown that the shear force due to blood circulation, chiefly at arterial pressures, is an important cause of endothelial dysfunction at these sites. 9 Still, arterial geometry and pressure are not sufficient to explain the localization of lesions, since major areas of high risk for atherosclerosis also occur away from the ostia and bifurcations 10 and some arteries subjected to normal arterial blood pressure are little affected by atherosclerosis. and the activity of acid cholesterol esterase 14 vary among vessels, and this variation could be related to differences in atherosclerosis susceptibility. A further aspect of arterial constitution that has been correlated with regional differences in the incidence of atherosclerosis is the degree of folding of the internal elastic membrane in humans, 15 which somehow reflects the amount of elastin in the vessel wall.Taken together, the results of these mostly recent studies show that focal metabolic and biochemical factors inherent in...

Composition changes in GAGs in strictured urethras could contribute to the noncompliant nature of urethral scar tissue and cause functional changes. These results may be useful for defining new targets for therapy for urethral stricture disease.

No abstract

The synthesis of proteoglycans involves steps that regulate both protein and glycosaminoglycan (GAG) synthesis, but it is unclear whether these two pathways are regulated by the same or different signaling pathways. We therefore investigated signaling pathways involved in platelet-derived growth factor (PDGF)-mediated increases in versican core protein and GAG chain synthesis in arterial smooth muscle cells (ASMCs). PDGF treatment of ASMCs resulted in increased versican core protein synthesis and elongation of GAG chains attached to the versican core protein. The effects of PDGF on versican mRNA were blocked by inhibiting either protein kinase C (PKC) or the ERK pathways, whereas the GAG elongation effect of PDGF was blocked by PKC inhibition but not by ERK inhibition. Interestingly, blocking protein synthesis in the presence of cycloheximide abolished the PDGF effect, but not in the presence of xyloside, indicating that GAG synthesis that results from PKC activation is independent from de novo protein synthesis. PDGF also stimulated an increase in the chondroitin-6-sulfate to chondroitin-4-sulfate ratio of GAG chains on versican, and this effect was blocked by PKC inhibitors. These data show that PKC activation is sufficient to cause GAG chain elongation, but both PKC and ERK activation are required for versican mRNA core protein expression. These results indicate that different signaling pathways control different aspects of PDGF-stimulated versican biosynthesis by ASMCs. These data will be useful in designing strategies to interfere with the synthesis of this proteoglycan in various disease states.

During testicular migration gubernacular connective tissue undergoes extensive remodeling and ultimately becomes an essentially fibrous structure rich in collagen and elastic fibers. Such changes should decrease the size of the gubernaculum and, thus, contribute to other forces that cause the testes to move toward the scrotum. In fact, because of the lack of smooth muscle cells, and the amount and organization of striated muscle cells, active contraction of the gubernaculum is less likely to be an important factor in testicular descent.

• Midshaft penile fragments were obtained and processed by routine histological techniques. Stereological analysis of collagen, elastic system fibres and smooth muscle was performed in 5-μ m sections by using a M42 test grid system.• Data were expressed as volumetric density (Vv; %). Collagen organization was evaluated by Picrosirius red staining under polarization. RESULTS• In the TA of diabetic rabbits, thickness increased by 88% ( P < 0.001) with an enhanced collagen turnover. Moreover, the elastic fibre content was 34% higher ( P < 0.001). In the CC of diabetics, collagen was diminished by 45% ( P < 0.001) with a more organized collagen.• The elastic fibres were decreased by 46% ( P < 0.001). Diabetes induced a 11% increase in CS collagen ( P < 0.024) with an enhanced collagen turnover.• Smooth muscle in the CC of diabetic rabbits was increased by 40% ( P < 0.001), whereas, in the CS, it was decreased by a similar amount ( P < 0.001). CONCLUSIONS• Penile tissues were affected differently by diabetes, possibly as a result of cellular heterogeneity.• These changes could have an impact on blood flow and tissue resistance, and therefore might adversely affect erection.

No abstract

During testicular migration gubernacular connective tissue undergoes extensive remodeling and ultimately becomes an essentially fibrous structure rich in collagen and elastic fibers. Such changes should decrease the size of the gubernaculum and, thus, contribute to other forces that cause the testes to move toward the scrotum. In fact, because of the lack of smooth muscle cells, and the amount and organization of striated muscle cells, active contraction of the gubernaculum is less likely to be an important factor in testicular descent.