Diez-Martinez, J. (Javier)
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- Nephrological approach to the blockade of the renin-angiotensin for treating hypertension(Elsevier, 2009) Diez-Martinez, J. (Javier)The renin-angiotensin system plays a key role in the regulation of blood pressure, and blockade of this system now forms a central part of strategies to reduce the risk for cardiovascular events in hypertensive patients, namely in those with renal disease and high risk. Blockade of the renin-angiotensin system with angiotensin converting enzyme inhibitors or angiotensin II type 1 receptor antagonists has proved effective in the treatment of hypertensive patients with or without renal disease, thus providing first-line therapy in the nephrological setting. Studies comparing the two classes of have shown that they appear to have similar efficacy though angiotensin II type 1 receptor antagonists are better tolerated. Although previous studies found that combinations of these two classes of drugs have greater antihypertensive and renoprotective effects than monotherapy, data from recent large trials suggest that combination therapy may be detrimental, namely in terms of renal complications.
- The stilbene disulfonic acid DIDS stimulates the production of TNF-alpha in human lymphocytes(Elsevier, 1992) Civeira, M.P. (María Pilar); Arrazola, A. (Arantxa); Larrea, E. (Esther); Medina, J.F. (Juan Francisco); Diez-Martinez, J. (Javier); Qian, C. (Cheng); Prieto, J. (Jesús); Garciandia, A. (Ana)Exposure of human peripheral blood mononuclear cells (PBMC) to the stilbene derivative DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid) (60 microM and above) significantly increased the release of tumor necrosis factor-alpha (TNF-alpha), as determined by TNF-alpha activity in the incubation media. When the TNF-alpha message was analyzed in PBMC by a reverse transcription/polymerase chain reaction (RT/PCR)-based procedure, it was found that incubation with DIDS (60 microM) was followed by a time-dependent accumulation of TNF-alpha mRNA. Measurements of intracellular pH showed that the presence of increasing concentrations of DIDS resulted in a progressive intracellular alkalinization of PBMC. It is suggested that the known DIDS effect of inhibiting transmembrane anion exchange, i.e., chloride/bicarbonate exchange, might play a role in the stimulation of TNF-alpha production by PBMC exposed to DIDS.
- Biochemical markers of myocardial remodelling in hypertensive heart disease(Oxford University Press, 2009) Arias, T. (Teresa); Lopez-Salazar, M.B. (María Begoña); Diez-Martinez, J. (Javier); Zudaire, A. (Amaia); Ravassa, S. (Susana); Gonzalez, A. (Arantxa); Hermida, N. (Nerea); Beaumont, J. (Javier)The intricate mechanisms responsible for the structural remodelling of the myocardium that facilitates the evolution to heart failure in hypertensive patients, namely in those with left ventricular hypertrophy, requires from clinicians the utilization of a multibiomarker approach for short-term and long-term stratification as well as prognostication of patients. Biochemical markers may also help to identify patients with no clinical evidence of hypertensive heart disease, and provide information about the need for more aggressive therapy during different stages of the disease, and potentially provide valuable biochemical data for the specialist. Although there is a continuous and complex interplay between biochemical and imaging markers, perhaps their use will also have the potential to modify the medical management of patients with hypertensive heart disease and therapeutic decision-making by tailoring a targeted therapy according to the predominant mechanism of myocardial remodelling. This article will review in brief the most relevant information on a panel of circulating molecules that may accomplish the criteria required to be considered as biochemical markers of the cardiomyocyte and non-cardiomyocyte structural changes that occur in the hypertensive myocardium.
- Galectin-3 inhibition with modified citrus pectin in hypertension(2021) Liu, E. (Elizabeth); Zampierollo, G. (Giovanna); Lopez-Salazar, M.B. (María Begoña); Diez-Martinez, J. (Javier); Lau, E.S. (Emily S.); Paniagua, S.M. (Samantha M.); Sarma, A.A. (Amy A.); Wang, T.J. (Thomas J.); Ho, J. E. (Jennifer H.)We investigated the effect of galectin-3 (Gal-3) inhibition with modified citrus pectin on markers of collagen metabolism in a proof-of-concept randomized placebo-controlled trial of participants with elevated Gal-3 levels and hypertension. Although higher Gal-3 levels were associated with female sex, diabetes, and reduced glomerular filtration rate in cross-sectional analyses, treatment with modified citrus pectin did not change collagen markers. The effect of Gal-3 inhibition among individuals with heart failure warrants further investigation. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
- A biomarker of myocardial fibrosis predicts long-term response to cardiac resynchronization therapy(Elsevier, 2006) Lopez-Salazar, M.B. (María Begoña); Gavira, J.J. (Juan José); Diez-Martinez, J. (Javier); Alegria, E. (Eduardo); Gonzalez, A. (Arantxa); Macias, A. (Alfonso); Garcia-Bolao, I. (Ignacio); Azcarate, P.M. (Pedro María)
- Altered cardiac expression of peroxisome proliferator-activated receptor-isoforms in patients with hypertensive heart disease(Oxford University Press, 2006) Goikoetxea-Lapresa, M.J. (María José); Querejeta, R. (Ramón); Lopez-Salazar, M.B. (María Begoña); Diez-Martinez, J. (Javier); Gonzalez, A. (Arantxa); Larman, M. (Mariano); Beaumont, J. (Javier)OBJECTIVE: To investigate whether cardiac expression of the nuclear peroxisome proliferator-activated receptor alpha (PPARalpha) is altered in patients with hypertensive heart disease (HHD). METHODS: We studied endomyocardial septal biopsies from 24 patients with essential hypertension divided into three groups: 6 without left ventricular hypertrophy (LVH) (HT group), 10 with LVH (LVH group), and 8 with LVH and heart failure (HF) (HF group). The expression of two PPARalpha isoforms (the native active and the truncated inhibitory) was analyzed by Western blot and reverse transcription polymerase chain reaction (RT-PCR), and two PPARalpha target genes were evaluated by RT-PCR. Histomorphological features were evaluated in a second myocardial sample from LVH and HF groups. RESULTS: Whereas the expression of native PPARalpha protein was lower (p<0.05) in LVH and HF groups than in the HT group, truncated PPARalpha protein was overexpressed (p<0.001) in the HF group as compared with LVH and HT groups. The mRNA expression of native and truncated PPARalpha was similar in the three groups of hypertensives. In addition, a progressive decrease (p for trend<0.05) in the two PPARalpha target genes mRNA expression was observed among HT, LVH and HF groups. The amount of truncated PPARalpha protein correlates directly with cardiomyocytes apoptosis and inversely with cardiomyocytes density in patients with HHD. In addition, the expression of truncated PPARalpha protein was directly correlated with left ventricular volumes, and inversely with ejection fraction in all hypertensives. CONCLUSIONS: These findings suggest that post-transcriptional regulation of PPARalpha isoforms is altered in patients with HHD, namely in those developing HF. An excess of the truncated inhibitory isoform may be involved in hypertensive left ventricular failure and remodeling.
- Association between matrix metalloproteinase-10 concentration and smoking in individuals without cardiovascular disease(Elsevier, 2008) Paramo, J.A. (José Antonio); Beloqui, O. (Óscar); Diez-Martinez, J. (Javier); Orbe, J. (Josune); Rodriguez, J.A. (José Antonio)INTRODUCTION AND OBJECTIVES: Smoking is an important cardiovascular risk factor whose underlying mechanism is incompletely understood. However, it has been suggested that alterations in the balance between synthesis and degradation of the extracellular matrix (ECM) may play a role. The aim of this study was to determine whether there is an independent association between smoking and the concentration of circulating metalloproteinases (MMPs) in individuals without cardiovascular disease. METHODS: Metabolic parameters, the carotid intima-media thickness (IMT), inflammatory markers (fibrinogen, C-reactive protein and interleukin-6), markers of endothelial damage (e.g., von Willebrand factor), and the concentration of MMP-1, -9 and -10 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were assessed in 400 asymptomatic individuals with cardiovascular risk factors. Subjects were divided into non-smokers (n=195), smokers (n=118) and former smokers (n=87). In addition, global cardiovascular risk was determined from PROCAM and REGICOR scores. RESULTS: Both MMP-1 and MMP-10 concentrations were significantly higher in smokers than non-smokers (P< .05 and P< .001, respectively), though there was no difference in the levels of MMP-9, TIMP-1, IMT and other inflammatory parameters. There were positive correlations between the MMP-10 concentration and PROCAM and REGICOR scores (P< .001). Multivariate analysis showed that there was still an association between smoking and the MMP-10 concentration after adjustment for age, sex and other cardiovascular risk factors (P< .001). Multiple regression analysis showed that smoking accounted for 28% of the variability in the MMP-10 concentration. CONCLUSIONS: There was an independent association between smoking and the MMP-10 concentration in asymptomatic individuals. This relationship between MMP-10 and the ECM may indicate a mechanism through which this MMP contributes to smoking-related atherosclerosis.
- A translational approach to myocardial remodelling(Oxford University Press, 2009) Diez-Martinez, J. (Javier); Ertl, G. (Georg)
- Serum soluble ST2 as a biochemical marker of acute heart failure: future areas of research(Elsevier, 2008) Diez-Martinez, J. (Javier)
- Increased collagen type I synthesis in patients with heart failure of hypertensive origin: relation to myocardial fibrosis(American Heart Association, 2004) Martinez-Ubago, J.L. (José L.); Sanchez, E. (Eloy); Querejeta, R. (Ramón); Lopez-Salazar, M.B. (María Begoña); Diez-Martinez, J. (Javier); Gonzalez, A. (Arantxa); Larman, M. (Mariano)BACKGROUND: We investigated whether increased collagen type I synthesis and deposition contribute to enhancement of myocardial fibrosis and deterioration of cardiac function in patients with hypertensive heart disease (HHD). METHODS AND RESULTS: We studied 65 hypertensives with left ventricular hypertrophy subdivided into 2 groups: 34 patients without heart failure (HF) and 31 patients with HF. Transvenous endomyocardial biopsies of the interventricular septum were performed to quantify the amount of fibrotic tissue and the extent of collagen type I deposition. The carboxy-terminal propeptide of procollagen type I (PIP), an index of collagen type I synthesis, was measured by radioimmunoassay in serum samples from the coronary sinus and the antecubital vein. Compared with normotensives, the amount of collagen tissue, the extent of collagen type I deposition, and coronary and peripheral PIP were increased (P<0.01) in the 2 groups of hypertensives. These parameters were also increased (P<0.01) in HF hypertensives compared with non-HF hypertensives. Coronary PIP was higher (P<0.01) than peripheral PIP in hypertensives but not in normotensives. The amount of collagen tissue was inversely correlated with the ejection fraction and directly correlated with both coronary and peripheral PIP in all hypertensives. CONCLUSIONS: These findings suggest that an excess of cardiac collagen type I synthesis and deposition may be involved in the enhancement of myocardial fibrosis that accompanies the development of HF in HHD. In addition, our data show that the heart secretes PIP via the coronary sinus into the peripheral circulation in patients with HHD. Thus, PIP determined in peripheral blood can be a useful marker of myocardial fibrosis in these patients.