Response to Letter to Editor
Response to “Plasma Homocysteine Levels and Endothelial Dysfunction in Cerebro- and Cardiovascular Diseases in the Metabolic Syndrome” Cristiana Catena,1 GianLuca Colussi,1 and Leonardo A. Sechi1
To the Editor: Tsuda commented on our recently published study1 in which we reported data obtained in 562 essential hypertensive patients showing that elevated plasma homocysteine levels are associated with the metabolic syndrome. We reported also that increasing homocysteine levels are associated with progressively greater prevalence of coronary heart and cerebrovascular disease. In another study,2 we have demonstrated that plasma homocysteine is directly related with the carotid artery intima-media thickness in patients with high blood pressure, suggesting a contribution of homocysteine to the earliest stages of the atherosclerotic process. In his letter, “Plasma Homocysteine Levels and Endothelial Dysfunction in Correspondence: Cristiana Catena (cristiana.
[email protected]). 1Hypertension Unit, Internal Medicine,
Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy.
Initially submitted August 11, 2015; date of first revision August 16, 2015; accepted for publication August 18, 2015; online publication September 14, 2015. doi:10.1093/ajh/hpv159 © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email:
[email protected]
Cerebro- and Cardiovascular Diseases in the Metabolic Syndrome,”3 Tsuda indicates the possibility that endothelial dysfunction and impaired nitric oxide bioavailability might mediate the untoward vascular effects of homocysteine. In fact, experimental studies have suggested many mechanisms that might explain the contribution of elevated circulating homocysteine to promotion of atherogenesis and progression of vascular damage. Among these mechanisms, endothelial damage with impaired endothelial vasodilatory response, proliferation of vascular smooth muscle cell, activation of monocytes and prothrombotic mediators, and lipid peroxidation might play a prominent role. These mechanisms might result from multiple biochemical reactions that are triggered by homocysteine and include auto-oxidation through the production of reactive oxygen species, nitrosylation by binding to nitric oxide, inhibition of transmethylations, and protein homocysteinylation. All these mechanisms are currently under debate and will deserve further investigation.4 Therefore, we agree with the comments of Tsuda, although in our study we did not have the opportunity to assess any of the markers of endothelial dysfunction and nitric oxide bioavailability in a reasonable number of patients, taking into
1490 American Journal of Hypertension 28(12) December 2015
account the large sample of recruited subjects and also considering that such assessments were beyond the scopes of our study. Inclusion of such assessments in future studies will surely provide important insight into the mechanisms that cause vascular damage in subjects with elevated plasma homocysteine.
DISCLOSURE
The authors declared no conflict of interest.
REFERENCES 1. Catena C, Colussi GL, Nait F, Capobianco F, Sechi LA. Elevated homocysteine levels are associated with the metabolic syndrome and cardiovascular events in hypertensive patients. Am J Hypertens 2015; 28:943–950. 2. Catena C, Colussi GL, Url-Michitsc M, Nait F, Sechi LA. Subclinical carotid artery disease and plasma homocysteine levels in patients with hypertension. J Am Soc Hypertens 2015; 9:167–175. 3. Tsuda K. Plasma homocysteine levels and endothelial dysfunction in cerebro- and cardiovascular diseases in the metabolic syndrome. Am J Hypertens 2015, in press. 4. Lai WK, Kan MY. Homocysteine-induced endothelial dysfunction. Ann Nutr Metab 2015; 67:1–12.
