Response to Junctional Adhesion Molecule-1 May Have a Wider Role in Cardiovascular Disease
We thank Cheung and Ong1 for their interesting insights into a possible wider role for junctional adhesion molecule-1 (JAM-1) in cardiovascular disease other than the novel function that we report of a sympathoexcitatory/prohypertensive role when over expressed in the nucleus tractus solitarii of normotensive rats.2 We would like to state that we fully support this idea based on the ubiquity of the overexpression of JAM-1 in the spontaneously hypertensive rat.
We would like to address 2 points that the authors have raised. First, regarding the issue of obesity and diabetes (metabolic syndrome) and JAM-1, as with hypertension, these diseases are associated with enhanced sympathetic vasoconstrictor traffic. Indeed, Grassi et al3 have suggested that overactivation of the sympathetic nervous system “represents the common underlying pathogenetic link among the various components of the metabolic syndrome.” This is based on evidence that the sympathetic nervous system plays a pivotal role in the chronic regulation of energy expenditure, basal metabolic rate, thermogenesis, plasma glucose levels, and arterial pressure. Moreover, Grassi et al3 stress the importance of reducing sympathetic nerve activity as a specific aim of therapeutic intervention for the metabolic syndrome. Thus, according to the idea of Grassi et al,3 we would suggest that JAM-1 may be involved in the development of the metabolic syndrome components via its central sympathoexcitatory action within, eg, the nucleus tractus solitarii. As stated by Cheung and Ong,1 the overexpression of JAM-1 found in other peripheral tissues now requires attention as to its contribution to the metabolic syndrome.
Second, Cheung and Ong1 mention that inflammation is involved in the pathogenesis of hypertension. We would agree with this statement. Our study clearly indicates that overexpression of JAM-1 within the nucleus tractus solitarii induces vascular inflammation as evidenced by the adherence of leukocytes.2 Vascular inflammation clearly exists within the spontaneously hypertensive rat, including inflamed vessels within the brain stem that may contribute to the sympathoexcitatory effects seen in hypertension. We speculate as to whether drug treatment strategy for essential hypertension should consider tackling this vascular inflammation. However, we are also intrigued that vascular inflammation is common to neurodegenerative diseases, including Alzheimer, and that drugs used to lower sympathetic nerve activity in hypertensive subjects, such as angiotensin-converting enzyme inhibitors, also improve cognition in patients with Alzheimer disease.4 Could there be commonality in the origin of these disease states? The type of vascular inflammation presented in the spontaneously hypertensive rat requires a thorough investigation before the hypothesis that vascular inflammation in the brain stem is a contributory factor for essential hypertension can be fully tested. Because JAM-1 overexpression is raised before the onset of hypertension in the spontaneously hypertensive rat,2 we propose that it may be a valuable prognostic indicator for high blood pressure. This remains to be tested, and these tests must now include humans. We conclude that JAM-1 may be a nodal point in the development of multiple diseases, which include inflammation of the vasculature and excessive sympathetic drive.
Cheung BMY, Ong KL. Junctional adhesion molecule-1 may have a wider role in cardiovascular disease. Hypertension. 2007; 50: e22.
Waki H, Liu B, Miyake M, Katahira K, Murphy D, Kasparov S, Paton JF. Junctional adhesion molecule-1 is upregulated in spontaneously hypertensive rats: evidence for a prohypertensive role within the brain stem. Hypertension. 2007; 49: 1321–1327.
Grassi G, Quarti-Trevano F, Seravalle G, Dell’oro R. Cardiovascular risk and adrenergic overdrive in the metabolic syndrome. Nutr Metab Cardiovasc Dis. In press.