Cardiovascular risk factors and arterial rigidity are similar in asymptomatic normocalcemic and hypercalcemic primary hyperparathyroidism.

OBJECTIVE: It is still uncertain whether mild primary hyperparathyroidism (PHPT) carries the same risk for increased cardiovascular (CV) morbidity as the more severe symptomatic form. In recent years, the even more subtle normocalcemic (NC) variant is being increasingly recognized. We sought to compare the prevalence of CV risk factors in patients with NC- and hypercalcemic (HC)-PHPT, and to examine whether they differ on a battery of non-invasive vascular parameters. DESIGN/SUBJECTS/METHODS: A retrospective study of two cohorts of patients with PHPT in a referral center: 32 subjects with NC-PHPT and 81 subjects with HC-PHPT, compared for the presence of clinical and biochemical risk factors, and CV morbidity. Non-invasive parameters of arterial stiffness (augmentation index; pulse wave velocity; and vascular compliance indices, C1 and C2) were extracted from the data of gender- and age-matched subsets of these patients, and were related to those of a group of matched control subjects. RESULTS: Despite a similar prevalence of hypertension (approximately 62%), hyperlipidemia (approximately 30%), and impaired glucose metabolism in both PHPT groups, CV or cerebrovascular disease was more common in the HC-PHPT group (24.7 vs 3.1%, P=0.007). Arterial stiffness parameters did not differ in the three groups, and were unrelated to serum calcium or parathyroid hormone concentration. CONCLUSIONS: NC-PHPT and HC-PHPT subjects exhibit similar high rates of traditional CV risk factors, and have comparable indices of arterial stiffness. The lower clinical CV morbidity observed with NC-PHPT remains unexplained, and requires confirmation. Until then, the CV risk associated with NC-PHPT should not be underestimated.

12S-lipoxygenase protein associates with alpha-actin fibers in human umbilical artery vascular smooth muscle cells.

The current study sets out to characterize the intracellular localization of the platelet-type 12S-lipoxygenase (12-LO), an enzyme involved in angiotensin-II induced signaling in vascular smooth muscle cells (VSMC). Immunohistochemical analysis of VSMC in vitro or human umbilical arteries in vivo showed a clear cytoplasmic localization. On immunogold electron microscopy, 12-LO was found primarily associated with cytoplasmic VSMC muscle fibrils. Upon angiotensin-II treatment of cultured VSMC, immunoprecipitated 12-LO was found bound to alpha-actin, a component of the cytoplasmic myofilaments. 12-LO/alpha-actin binding was blocked by VSMC pretreatment with the 12-LO inhibitors, baicalien or esculetine and the protein synthesis inhibitor, cycloheximide. Moreover, the binding of 12-LO to alpha-actin was not associated with 12-LO serine or tyrosine phosphorylation. These observations suggest a previously unrecognized angiotensin-II dependent protein interaction in VSMC through which 12-LO protein may be trafficked, for yet undiscovered purposes towards the much more abundantly expressed cytoskeletal protein alpha-actin.