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Updated: Aug 16, 2026
An Ex Vivo Method for Time-Lapse Imaging of Cultured Rat Mesenteric Microvascular Networks
Published on: February 9, 2017
Actions of lipoproteins in cultured human mesangial cells: modulation by mitogenic vasoconstrictors
E F Gröne1, H E Abboud, M Höhne
1Department of Pathology, University of Göttingen, Federal Republic of Germany.
Abstract:
Recent studies have suggested that hypercholesterolemia may aggravate glomerulosclerosis. Mesangial cells actively participate in this process. To elucidate mechanisms by which lipids act on human mesangial cells (HMC), we measured the receptor-specific uptake of apolipoprotein (Apo) B- and Apo B- and E-containing lipoproteins in the presence and absence of growth factors and studied the growth-related mechanisms in HMC after exposure to low-density lipoprotein (LDL). Human LDL and very low density beta-lipoprotein (beta-VLDL) isolated from cholesterol-fed rabbits were bound, internalized, and degraded by a receptor-specific mechanism (dissociation constants for degradation LDL 30.0 and for beta-VLDL 4.1 micrograms protein/ml medium). Maximal capacities were 30-50% of those of human fibroblasts. Acetylated and copper-oxidized LDL were not taken up specifically, suggesting no active scavenger-receptor activity. Preexposure to endothelin-1 (5 x 10(-7) M) and platelet-derived growth factor (PDGF A, B, 83 x 10(-12) M) for 16 or 15 h, respectively, doubled the uptake of LDL by HMC. In addition, PDGF synergized with LDL in stimulating DNA synthesis. Exposure of HMC to LDL resulted in a transient elevation of mRNA that encodes c-fos and c-jun, with a maximal effect seen after 30-60 min. In addition, PDGF A- and B-chain mRNAs were transiently elevated, peaking at 3 h in response to LDL (25 micrograms protein/ml medium) and continued to increase in a concentration-dependent manner (25-75 micrograms protein/ml medium). These data demonstrate that HMC take up lipoproteins via a receptor-specific mechanism with a high affinity for Apo E-containing lipoproteins which are often found in plasma of patients with renal disease. Vasoconstrictor and mitogenic peptides enhance lipoprotein receptor activity and have a synergistic effect on the mitogenic effect of LDL. LDL stimulates a number of growth-related genes. These data suggest that lipoproteins may play a critical role in mediating mesangial cell hypertrophy or proliferation, events intimately involved in the development of glomerulosclerosis.
Insights
High cholesterol (hypercholesterolemia) may worsen glomerulosclerosis by affecting human mesangial cells (HMC). Lipoproteins, like low-density lipoprotein (LDL), are taken up by HMC, influencing their growth and potentially contributing to kidney disease.
Area of Science:
- Nephrology
- Cell Biology
- Lipid Metabolism
Background:
- Hypercholesterolemia is increasingly linked to the progression of glomerulosclerosis.
- Mesangial cells play a crucial role in the pathogenesis of glomerulosclerosis.
- Understanding lipid interactions with mesangial cells is vital for elucidating disease mechanisms.
Purpose of the Study:
- To investigate the mechanisms of lipoprotein uptake by human mesangial cells (HMC).
- To examine how growth factors influence lipoprotein uptake in HMC.
- To explore the effects of low-density lipoprotein (LDL) on HMC growth-related gene expression.
Main Methods:
- Measured receptor-specific uptake and degradation of apolipoprotein (Apo) B- and Apo B/E-containing lipoproteins in HMC.
- Assessed the impact of endothelin-1 and platelet-derived growth factor (PDGF) on LDL uptake.
- Analyzed the expression of growth-related genes (c-fos, c-jun, PDGF A/B chains) in HMC following LDL exposure.
Main Results:
- HMC exhibit receptor-specific uptake of LDL and very low-density beta-lipoprotein (beta-VLDL) with high affinity for Apo E-containing lipoproteins.
- Growth factors (endothelin-1, PDGF) significantly enhance LDL uptake and synergize with LDL to stimulate HMC DNA synthesis.
- LDL exposure induces transient elevation of c-fos, c-jun, and PDGF A/B chain mRNAs in HMC, indicating activation of growth pathways.
Conclusions:
- Lipoproteins are internalized by HMC via a specific receptor mechanism, particularly those containing Apo E.
- Growth factors modulate lipoprotein receptor activity and potentiate the mitogenic effects of LDL on HMC.
- Lipoprotein-induced activation of growth-related genes suggests a role in mesangial cell hypertrophy/proliferation and glomerulosclerosis development.
