Abstract 1708: Primary Amyloidosis Light Chains Impair Endothelium-Dependent Vasodilation in Human Arterioles
Primary systemic AL amyloidosis (AL) can be a fatal disease and the mechanism underlying vascular injury from amyloid light chains (LC) is unknown.
Aims: To measure endothelium-dependent and endothelium-independent vasoreactivity and oxidative stress in isolated human adipose arterioles following exposure to LC.
Methods: LC was isolated from the urine of two AL patients using dialysis and lyophilization. Discarded human visceral fat arterioles from 8 patients without vascular disease undergoing routine thoracic or abdominal surgery were cannulated and pressurized to 60 mm Hg. Internal vessel diameter was measured using video micrometer. After pre-constriction with endothelin, vascular reactivity to acetylcholine (ACh, 10−9 to 10−4 M) and papaverine (P, 10−4 M) before and following 30 minutes intraluminal exposure to LC (20 μg/mL) was measured as % of maximum diameter. Separately, vessels were exposed to vehicle or LC and H2O2 was assessed using 2′7′-dichlorodihydrofluorescein method and O2· was assessed using hydroethidine method.
Results: see figure⇓. Exposure to LC led to significant impairment in Ach (endothelium-dependent) mediated vasodilation (Fig 1A⇓). There was a non-significant trend of impaired response to papaverine (smooth muscle dependent dilation) (Figure 1A⇓, P). There is increased O2· (2.4±0.6x control, Fig. 1 B and C⇓) and H2O2 (1.6±0.2x control, Fig. 1 D and E⇓) in the arterioles following LC exposure.
Conclusions: Brief exposure to amyloid LC results in impairment in endothelium-mediated vasodilation in human adipose arterioles. The underlying mechanism for the endothelial dysfunction may be induction of oxidative stress.