Effect of glycated LDL on microvascular tone in mice: a comparative study with LDL modified in vitro or isolated from diabetic patients.
OBJECTIVE
In vitro studies have suggested that glycation of LDL might be implicated in diabetic microangiopathy. We therefore investigated the in vivo effects of LDL glycated in vitro on the mouse skeletal muscle arteriolar tone. Since glycation naturally occurs during diabetes, we also tested the effects of LDL isolated from diabetic patients.


METHODS
In anaesthetized mice, the spinotrapezius muscle microcirculation was observed, in situ, using the orthogonal polarization spectral imaging technology. The diameter of terminal (<20 microm) and small arterioles (20-40 microm) was measured before and after a bolus intravenous injection of glycated LDL followed by a continuous perfusion (115 micro g/kg/min).


RESULTS
A slight decrease of terminal and small arterioles diameter (<10%) was observed with native LDL and LDL isolated from healthy subjects. In contrast, mildly glycated LDL induced a clear vasoconstriction of arterioles (>15%), which was further increased when highly glycated LDL was perfused (>22%). LDL isolated from diabetic patients mimicked the vasoconstriction obtained with in vitro mildly glycated LDL, which underwent similar glycation as those isolated from diabetic patients.


CONCLUSIONS
Our results show in vivo that acute perfusion of both types of glycated LDL (artificially or naturally modified), cause major microvascular modification by enhancing arteriolar tone in skeletal muscle. These findings highlight a new role of glycated LDL at the level of microvessels. We suggest that glycation of LDL could contribute to the impaired vascular reactivity observed in diabetes.
Nivoit
P
P
Diabetic Microangiopathy Research Unit, MERCK Santé-INSERM UMR 585 INSA-Lyon, Villeurbanne, Cedex, France. pierre.nivoit@insa-lyon.fr
Wiernsperger
N
N
Moulin
P
P
Lagarde
M
M
Renaudin
C
C
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D003920:Diabetes Mellitus / Q000097:blood*; D017127:Glycation End Products, Advanced; D006031:Glycosylation; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D013045:Species Specificity; D000093844:Glycated Proteins
D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; C031797:glycated lipoproteins, LDL; D000093844:Glycated Proteins