Can low density lipoprotein influence microvascular caliber?

The intracellular free calcium concentration ([Ca2+]i) plays an important role in the regulation of vascular tone. In vascular smooth muscle cells (VSMCs) LDL causes changes in vascular tone by increasing [Ca2+]i. Pericytes are regarded as the microvascular counterpart of VSMCs and implicated in the regulation of microvascular cell biology under normal and pathological conditions (e.g., diabetes mellitus, arterial hypertension, arteriosclerosis). For this reason pericytes and VSMCs were compared in their ability to increase [Ca2+]i after stimulation with LDL. Single VSMCs and pericytes were loaded with 2 microM of the Ca2+-sensitive dye Indo-1/AM. Fluorescence was recorded at 405 nm (Ca2+-bound) and 485 nm (Ca2+-free). Cells in suspension were loaded with 2 microM of the calcium ionophore FURA-2 AM (excitation wavelengths: 340 and 380 nm, emission 505 nm). Basal [Ca2+]i levels were significantly higher in single pericytes (165 +/- 38 nmol/L, n = 41) than in VSMCs (150 +/- 39 nmol/L, n = 40, P = 0.0038). In cell suspensions the following values were obtained: Pericytes (113 +/- 27 nmol/L, n = 36) and VSMCs (109 +/- 26 nmol/L, n = 28), which are statistically not significant. For all concentrations of LDL used (except at 1 microg/ml n-LDL), the increase above basal values was significant and both cell types showed a clear dose-dependent reaction pattern. This study shows for the first time that pericytes and VSMCs increase their [Ca2+]i in a similar way after LDL stimulation. In analogy to aortic smooth muscle cells, our results indicate that LDL mediated [Ca2+]i changes in pericytes in the microvascular bed may cause vasoconstriction leading to impairment of blood flow in the microvasculature.