Minimally Modified LDL-Induced Impairment of Endothelium-Dependent Relaxation in Small Mesenteric Arteries of Mice

Abstract

Minimally modified low-density lipoprotein (mmLDL) is a well-known risk factor for cardiovascular diseases. The present study was designed to investigate the role of mmLDL in the endothelium-dependent relaxation of mouse mesenteric arteries. A sensitive myograph system was employed to examine the endothelial function of mesenteric arteries. mRNA and protein expression levels were determined using real-time PCR and Western blotting, respectively. The ultramicrostructure of mesenteric vascular beds was investigated using a transmission electron microscope. The results showed that mmLDL significantly impaired the acetylcholine-induced (3 × 10−¹⁰ to 1 × 10−⁴<smlcap>M</smlcap>) endothelium-dependent relaxation of mouse mesenteric arteries with markedly reduced pIC₅₀ (p < 0.05) and R_max values (p < 0.001). In addition, mmLDL increased the levels of superoxide production and nitrotyrosine concentration and impaired the endothelial microstructure with decreased K_Ca3.1 and K_Ca2.3 expression. In conclusion, mmLDL increases superoxide and nitrotyrosine levels, damages endothelial microstructure with decreased K_Ca3.1 and K_Ca2.3 expression, and ultimately attenuates relaxation mediated by nitric oxide- and endothelium-derived hyperpolarizing factor.

Minimally modified low-density lipoprotein upregulates the ETB and α1 receptors in mouse mesenteric arteries in vivo by activating the PI3K/Akt pathway

“…Minimally modified low‐density lipoprotein was prepared according to the literature . LDL at 0.2 mg/ml was added to EDTA‐free phosphate‐buffered saline (PBS), which contained 1 μ m FeSO 4 , for a 96‐h dialysis at 4°C.…”

“…After the animal was sacrificed, the mesenteric arteries were isolated, and the constriction of the arterious ring was detected according to the methods described in the literature . Under a microscope, the tissue around the vessel was removed.…”

Cardiovascular bioimaging of nitric oxide: Achievements, challenges, and the future

“…One of the first identified manifestations of endothelial dysfunction is the impairment of NO‐dependent vasodilation in response to acetylcholine 32 . In particular, NO inhibits oxidation of low‐density lipoproteins (LDL), 33 a known promoter of atherosclerosis and LDL impairs NO‐mediated arterial relaxation 34 . In comparison, high‐density lipoproteins (HDL), a known inhibitor of atherosclerosis enhances NO production via apolipoprotein A‐I mediated action on scavenger receptor class B Type 1 (SR‐B1) function by changing eNOS localization 35 .…”

“…32 In particular, NO inhibits oxidation of low-density lipoproteins (LDL), 33 a known promoter of atherosclerosis and LDL impairs NO-mediated arterial relaxation. 34 In comparison, high-density lipoproteins (HDL), a known inhibitor of atherosclerosis enhances NO production via apolipoprotein A-I mediated action on scavenger receptor class B Type 1 (SR-B1) function by changing eNOS localization. 35 A deficiency of NO leads to increased platelet aggregation and smooth muscle proliferation in vascular tissues.…”

The Class III PI3K/Beclin-1 Autophagic Pathway Participates in the mmLDL-Induced Upregulation of ETA Receptor in Mouse Mesenteric Arteries

“…To investigate the effect of mmLDL on mouse arteriomesenteric ET A receptors, the mmLDL group received 8 injections of 1 mg/kg mmLDL via the caudal vein at an injection interval of 12 h. At 96 h, the animals were killed via cervical dislocation after eyeball blood was drawn; then, the mesenteric arteries were collected for subsequent experiments [11][12][13]. e normal saline (NS) group and the LDL group were given the same dosage of physiological saline and LDL, respectively.…”