Low density lipoprotein receptors mediate intracellular calcium signals in microalbuminuric hypertensives.
Hyperlipidemia is an established risk factor for progressive renal damage and proteinuria. Platelets and vascular smooth muscle cells (VSMC) are known to possess low density lipoprotein (LDL) cholesterol receptors. We used platelet LDL receptors to investigate the hypothesis that elevated lipids could activate intracellular calcium [Ca2+]i signals, leading to altered vascular tone and permeability. We divided essential hypertensives into microalbuminuric positive (MA+) and negative (MA-) groups and measured baseline and LDL stimulated levels of [Ca2+]i. The MA+ group demonstrated a significantly higher mean baseline [Ca2+]i level (119.0 +/-24.5 v 86.2 +/- 25.4 micromol/mL, P = .001). The MA+ group also displayed greater elevations in [Ca2+]i levels after stimulation with LDL in concentrations of 10 and 25 microg/mL (100.9 +/- 54.8 v 40.9 +/- 20.2, P = .04 and 111.6 +/- 51.0 v 52.9 +/- 39.9 micromol/mL, P = .03, respectively). Our data indicate that hypertensive patients with early glomerular capillary injury display exaggerated influx of [Ca2+]i after LDL receptor stimulation. Heightened LDL receptor sensitivity may facilitate LDL mediated [Ca2+]i signals, leading to increased VSMC tone and proliferation and progressive renal disease.
Fong
R L
RL
Department of Internal Medicine, King/Drew Medical Center, Los Angeles, CA 90059, USA.
Vadgama
J V
JV
Laguer
M R
MR
Ward
H J
HJ
D000328:Adult; D000419:Albuminuria / Q000150:complications / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications; D006973:Hypertension / Q000150:complications / Q000378:metabolism*; D008875:Middle Aged; D011507:Proteinuria / Q000150:complications; D011973:Receptors, LDL / Q000378:metabolism*; D015398:Signal Transduction
D011973:Receptors, LDL; D002118:Calcium