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Vascular regression in the kidney: changes in 3D vessel structure with time post-irradiation
Soudeh Mostaghimi1, Shima Mehrvar2, Farnaz H Foomani3
1Department of Biomedical Engineering at University of California, Irvine, CA 92697, USA.
Abstract:
Though angiogenesis has been investigated in depth, vascular regression and rarefaction remain poorly understood. Regression of renal vasculature accompanies many pathological states such as diabetes, hypertension, atherosclerosis, and radiotherapy. Radiation decreases microvessel density in multiple organs, though the mechanism is not known. By using a whole animal (rat) model with a single dose of partial body irradiation to the kidney, changes in the volume of renal vasculature were recorded at two time points, 60 and 90 days after exposure. Next, a novel vascular and metabolic imaging (VMI) technique was used to computationally assess 3D vessel diameter, volume, branch depth, and density over multiple levels of branching down to 70 µm. Four groups of rats were studied, of which two groups received a single dose of 12.5 Gy X-rays. The kidneys were harvested after 60 or 90 days from one irradiated and one non-irradiated group at each time point. Measurements of the 3D vasculature showed that by day-90 post-radiation, when renal function is known to deteriorate, total vessel volume, vessel density, maximum branch depth, and the number of terminal points in the kidneys decreased by 55%, 57%, 28%, and 53%, respectively. Decreases in the same parameters were not statistically significant at 60 days post-irradiation. Smaller vessels with internal diameters of 70-450 µm as well as large vessels of diameter 451-850 µm, both decreased by 90 days post-radiation. Vascular regression in the lungs of the same strain of irradiated rats has been reported to occur before 60 days supporting the hypothesis that this process is regulated in an organ-specific manner and occurs by a concurrent decrease in luminal diameters of small as well as large blood vessels.
Insights
Radiation exposure causes significant renal vascular regression, decreasing vessel volume and density by 90 days post-irradiation. This study reveals organ-specific vascular changes following radiation, impacting both small and large blood vessels.
Area of Science:
- Radiology and Imaging
- Vascular Biology
- Renal Pathophysiology
Background:
- Vascular regression and rarefaction are poorly understood processes, unlike angiogenesis.
- Renal vasculature regression is associated with various pathologies including diabetes, hypertension, atherosclerosis, and radiotherapy.
- Radiation is known to decrease microvessel density, but the underlying mechanisms remain unclear.
Purpose of the Study:
- To investigate the effects of radiation on renal vasculature volume and structure.
- To understand the temporal dynamics of radiation-induced vascular changes in the kidney.
- To explore the organ-specific nature of radiation-induced vascular regression.
Main Methods:
- A whole-animal rat model was used with a single dose of partial body irradiation to the kidney.
- Vascular and Metabolic Imaging (VMI) technique was employed to computationally assess 3D vasculature.
- Kidneys were harvested at 60 and 90 days post-irradiation for detailed analysis of vessel diameter, volume, branch depth, and density.
Main Results:
- By 90 days post-irradiation, total vessel volume, vessel density, maximum branch depth, and terminal points decreased by 55%, 57%, 28%, and 53%, respectively.
- These significant decreases were not observed at 60 days post-irradiation.
- Both small (70-450 µm) and large (451-850 µm) blood vessels showed decreased diameters by 90 days.
Conclusions:
- Radiation induces significant renal vascular regression, characterized by decreased vessel volume and density, primarily evident by 90 days post-exposure.
- The observed vascular regression in the kidneys supports the hypothesis of organ-specific regulation of this process.
- Radiation-induced vascular regression involves a concurrent reduction in the luminal diameters of both small and large blood vessels.
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