Response to Association of Increased Plasma Cardiotrophin-1 With Left Ventricular Mass Indexes in Normotensive Morbid Obesity
We read with interest the letter by Malavazos et al1 providing data concerning the potential involvement of cardiotrophin-1 (CT-1) in obesity-related left ventricular hypertrophy (LVH). They found that plasma CT-1 was higher in obese normotensive women with eccentric LVH than in normal-weight normotensive women without LVH. Thus, the authors have gathered evidence that an excess of CT-1 may be associated with LVH in the absence of pressure overload (eg, hypertension).
The association between obesity and LVH has been well established by a number of epidemiological and clinical studies. Although the hemodynamic factor (ie, volume overload) remains as the main pathogenetic link between obesity and exaggerated LV growth, recent experimental data suggest that some cytokines released by a multiplicity of tissues, namely, the adipose tissue (ie, leptin), may produce cardiomyocyte hypertrophy through multifaceted cell signaling mechanisms.2 Of interest, greatly increased levels of this cytokine are observed in obese patients independent of the presence or absence of hypertension.
Recently, we reported that CT-1 gene and protein expression progressively increased along with the differentiation time from preadipocyte to mature adipocyte in murine 3T3.L1 cells.3 mRNA and protein CT-1 expression were also demonstrated in human adipose biopsies. Importantly, immunostaining showed positive staining in human adipocytes. In addition, we found increased CT-1 serum levels in patients with the metabolic syndrome (MetS) compared with control subjects. Of interest, whereas circulating levels of CT-1 were higher in MetS patients with obesity than in MetS patients without obesity, no differences in this parameter were observed between MetS patients with hypertension compared with MetS patients without hypertension. Collectively, these data suggest that adipose tissue can be a source of CT-1, which could account for the high circulating levels of this cytokine found in patients with obesity and the MetS.
Taken together, the data by Malavazos et al1 and those from our group raise the hypothesis that the excess of adipose tissue present in normotensive obese people may contribute to exaggerated left ventricular growth in these patients through increased synthesis and release of CT-1 and probably other adipokines. Further studies are required to definitively prove this possibility.
Sources of Funding
This work was funded through the agreement between the Foundation for Applied Medical Research (FIMA) and UTE project CIMA, the red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares (RECAVA) from the Instituto de Salud Carlos III, Ministry of Health, Spain (grant RD06/0014/0008), and the European Union (InGenious HyperCare, grant LSHM-CT-2006-037093).
Malavazos AE, Ermetici F, Morricone L, Delnevo A, Coman C, Ambrosi B, Coersi MM. Association of increased plasma cardiotrophin-1 with left ventricular mass indexes in normotensive morbid obesity. Hypertension. 2008; 51: e8–e9.
Natal C, Fortuño MA, Restituto P, Colina I, Díez J, Varo N. Cardiotrophin-1 is expressed in adipose tissue and upregulated in the metabolic syndrome. Am J Physiol Endoc Metab. In press.