Endothelial dysfunction precedes C-fiber abnormalities in primary (AL) amyloidosis.
Primary (AL; immunoglobulin light-chain associated) amyloidosis is characterized by the deposition of pathological proteins in the extracellular matrix of tissues and organs. Autonomic and sensory peripheral neuropathy is a common feature of this disorder. The pathogenesis of the neuropathy is poorly defined. The aims of this study were to investigate vascular and neural function in the cutaneous microcirculation of AL amyloidosis patients. Seven patients with AL amyloidosis and controls were studied. Acetylcholine and sodium nitroprusside were iontophoresed into the forearm skin. Endothelial, smooth muscle, and C-fiber-mediated cutaneous blood flow (CuBF) were recorded by laser Doppler flowmetry. Endothelial vasodilation in the forearm skin was attenuated in AL amyloidosis patients (p = 0.007). Maximum endothelium-mediated CuBF in the patient group was reduced (p = 0.047). No group differences could be detected in the C-fiber response or smooth muscle vasodilation (p value not significant). Maximum C-fiber and endothelium-independent CuBF did not differ between the two groups (p value not significant). Early in the disease, AL amyloidosis patients present with impaired endothelial function. At this stage, C-fiber and smooth muscle function are still preserved. These data suggest that endothelial abnormalities precede and may contribute to the pathogenesis of the neuropathy associated with AL amyloidosis.
Berghoff
Martin
M
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Kathpal
Madeera
M
Khan
Faisal
F
Skinner
Martha
M
Falk
Rodney
R
Freeman
Roy
R
D000328:Adult; D000686:Amyloidosis / Q000378:metabolism* / Q000503:physiopathology*; D015992:Body Mass Index; D001831:Body Temperature; D004730:Endothelium, Vascular / Q000502:physiology; D005110:Extracellular Space / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000502:physiology; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism / Q000502:physiology*; D012867:Skin / Q000098:blood supply / Q000378:metabolism; D034941:Upper Extremity / Q000503:physiopathology