Wall Remodeling after Wall Shear Rate Normalization in Rat Mesenteric Arterial Collaterals

Abstract

Previous studies have demonstrated endothelial and smooth muscle hyperplasia occur during arterial luminal expansion associated with elevation of arterial wall shear rates. The current study investigated whether remodeling induced by elevated wall shear would ultimately result in a vessel with intimal and medial cell densities and other wall characteristics similar to control arteries. A rat mesenteric model was used in which collateral wall shear is restored to normal 4 weeks after arterial occlusion. Twelve weeks after shear elevation, paired in vivo measurements indicated that the maximum collateral inner diameter was increased 27–75%. Morphometric evaluation of collateral cross sections indicated that, relative to control arteries, luminal and medial areas were increased 79 ± 22 and 56 ± 15%. Collateral medial cell density was decreased (1.12 ± 0.044 vs. 1.35 ± 0.005 nuclei/1,000 µm²) but intimal cell density was similar (2.86 ± 0.166 vs. 2.49 ± 0.102 nuclei/100 µm luminal perimeter). Medial thickness to radius ratio was also similar between control and collateral arteries. Thus, for the wall characteristics evaluated, there are many similarities between enlarged collaterals and control arteries. Comparison of nuclear numbers in arterial cross sections of the current and previous studies suggest that intimal and medial cellular regression is correlated with a decrease in wall shear force toward normal levels.

Impaired collateral development in mature rats

“…After contrast enhancement, the luminal area, luminal area ϩ intimal area, and luminal ϩ intimal ϩ medial areas were determined by image analysis with gray level thresholding to select only the region to be measured. Previous measurements performed in this manner (6) have confirmed that this method provided results similar to manual tracing. The medial area (M) was calculated as follows:…”

“…Wall shear level is increased at this location (Table 1), and the rate and magnitude of expansion is correlated with the shear stimulus (38). The observations that arterial luminal expansion in this model occurs where wall shear is elevated, is correlated with the degree of shear elevation, and ceases after wall shear rate is normalized (6,38,40,41) suggest that wall shear is important at least as a molding influence if not as the primary stimulus. For these reasons, we consider the luminal expansion observed in these collaterals to be flow or shear mediated.…”

“…After the final diameter measurements at day 7, the vessels were prepared for histological evaluation as previously described (6,40). To preserve the arteries, a cotton suture was placed around the bowel segment containing the collateral-dependent region and adjacent arteries supplying normal tissue.…”

Smooth Muscle Cell Changes During Flow-Related Remodeling of Rat Mesenteric Resistance Arteries

“…The peak at day 8 preceded the increase in CSA, consistent with the expression of PCNA preceding hypertrophy compared with CSA also observed by Tulis et al, 22 although this appeared at an earlier time point (days 3 through 7). The late peak of PCNA seen at day 32 could be related to a later phase of remodeling appearing beyond 4 weeks, as observed by Fath et al 32 A regulation of the balance between cell proliferation and cell death may be the most important mechanism for remodeling, as has been suggested for embryonic development and normal tissue homeostasis (for review, see Best et al 33 and Hamet et al). 34 This is supported by the present study, where apoptosis determined by DNA laddering was more frequent in both the LF and HF arteries compared with control ( Figure 4B).…”

Chronic N G -Nitro- l -Arginine Methyl Ester Treatment Does Not Prevent Flow-Induced Remodeling in Mesenteric Feed Arteries and Arcading Arterioles

“…Two weeks of altered blood flow induced milder changes in external diameters and medial area compared with the previous study. Nonetheless, inasmuch as Unthank and colleagues 7,26 have shown that flow alterations lead to an initial abrupt change in vascular structure (within 1 week) followed by a slower adaptation over the subsequent months, the 2-week alteration is sufficiently long for examining mechanisms responsible for earlier structural remodeling in this model. Ligated arteries displayed significantly reduced circumferential distensibility compared with control arteries, despite the reduction in medial mass.…”