Peripheral Blood MicroRNA-21 as a Predictive Biomarker for Heart Failure With Preserved Ejection Fraction in Old Hypertensives.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a major health issue with high morbidity and mortality. The epidemiology and the factors that cause HFpEF have not been fully clarified, while accurate predictive biomarkers are lacking. Our aim was to determine whether levels of microRNA-21 (miR-21) in peripheral blood monocytes, which play a critical role in many pathophysiological pathways of hypertensive heart disease, can predict the occurrence of HFpEF in older hypertensives, as well as the associated mortality and morbidity. METHODS: We enrolled 151 elderly patients >60 years old with essential hypertension but without HF at baseline. miRs expression levels in peripheral blood mononuclear cells had been quantified by real-time reverse transcription polymerase chain reaction. RESULTS: During a median follow-up of 8.2 years, 56 patients (37%) had an event. Levels of miR-21 in peripheral mononuclear blood cells proved to be significantly associated with the occurrence of HFpEF. More specifically, the median HFpEF-free period was 110 months for those with miR-21 >2.1 and 114 months for those with miR-21 <2.1. In addition, multivariate analysis showed that miR-21 (hazard ratio 11.14), followed by hemoglobin (Hg) (hazard ratio 0.56 for Hg >13.6 g/dl, a 45% risk reduction), were independent and the most significant predictors of HFpEF events. CONCLUSIONS: miR-21 levels in peripheral blood monocytes are associated with the development of future HFpEF. Our findings may alter the risk models of HFpEF and support the rationale for further research into the modulation of miRs as biomarkers and treatment targets for HFpEF.

Differences in MicroRNA Expression in Pericoronary Adipose Tissue in Coronary Artery Disease Compared to Severe Valve Dysfunction.

Pericoronary adipose tissue (PCAT) is a source of microRNAs (miRs) that act as messengers for intercellular communication. We investigated whether the PCAT surrounding significant coronary atherosclerotic lesions shows specific miR expression patterns compared with PCAT surrounding plaque-free segments. We included 49 patients with 3-vessel coronary artery disease (CAD) and 19 patients with severe valvular disease but no CAD, who underwent elective cardiac surgery. The PCAT was harvested from two sites: adjacent to a significant atherosclerotic coronary lesion and from plaque-free segments. miR-133a, miR-21, miR-26b, miR-9, and miR-143 levels in PCAT cells were quantified by real-time reverse transcription polymerase chain reaction (data expressed as arbitrary units). Expression of miR-133, miR-21, and miR-26b in adipose tissue at a site without atherosclerotic lesion was much lower in patients with CAD than in those without CAD (0.82 ± 1.37 vs 1.86 ± 0.52, P < .001, 0.45 ± 1.3 vs 1.51 ± 1.11, P < .001, 0.3 ± 1.25 vs 1.2 ± 0.73, P = .02, respectively). In addition, miR-133, miR-21, and miR-143 in CAD patients showed significantly greater expression in PCAT from atherosclerotic lesion compared with plaque-free segments (1.32 ± 0.96 vs 0.82 ± 0.37 (P = .011), 0.91 ± 1.7 vs 0.3 ± 1.25 (P = .012), 1.2 ± 1.59 vs 0.43 ± 0.54 (P < .001), respectively). Our findings open new perspectives for the role of PCAT in the pathophysiology of atherosclerosis and should be further investigated.

Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Cardiac Structural and Electrical Remodeling: From Myocardial Cytology to Cardiodiabetology.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have changed the clinical landscape of diabetes mellitus (DM) therapy through their favourable effects on cardiovascular outcomes. Notably, the use of SGLT2i has been linked to cardiovascular benefits regardless of DM status, while their pleiotropic actions remain to be fully elucidated. What we do know is that SGLT2i exert beneficial effects even at the level of the myocardial cell and that these are linked to an improvement in the energy substrate, resulting in less inflammation and fibrosis. SGLT2i ameliorates myocardial extracellular matrix remodeling, cardiomyocyte stiffness and concentric hypertrophy, achieving beneficial remodeling of the left ventricle with significant implications for the pathogenesis and outcome of heart failure. Most studies show a significant improvement in markers of diastolic dysfunction along with a reduction in left ventricular hypertrophy. In addition to these effects, there is electrophysiological remodeling, which explains initial data suggesting that SGLT2i have an antiarrhythmic action against both atrial and ventricular arrhythmias. However, future studies need to clarify not only the exact mechanisms of this beneficial functional, structural, and electrophysiological cardiac remodeling but also its magnitude to determine whether this is a class or a drug effect.

Long-term prognostic value of myocardin expression levels in non-ischemic dilated cardiomyopathy.

The mortality of patients with non-ischemic dilated cardiomyopathy (NIDCM) remains substantial. We evaluated gene expression levels of myocardin, an early cardiac gene, in the peripheral blood cells of NIDCM patients as a prognostic biomarker in their long-term outcome and mortality from congestive HF (CHF). We retrospectively analyzed 101 consecutives optimally treated NIDCM patients of Cretan origin who were enrolled from the HF clinic of our hospital from November 2005 to December 2008. Our patient data were either taken from their medical files or recorded during visits to the HF unit or hospitalizations. Follow-up was carried out by telephone interview and by accessing information from general practitioners and cardiologists in private practice. The median follow-up period was 8 years (mean follow-up 7 ± 3.4 years). The overall mortality during follow-up was 61.4%, while mortality due to congestive heart failure (CHF) was 49.5%. Higher CHF and all-cause mortality were observed in patients with myocardin levels < 14.26 (p < 0.001 for both CHF and all-cause mortality). A multivariate Cox regression analysis showed that myocardin level of expression had independent significant prognostic value for the risk of death from CHF (HR 14.5, 95% confidence interval (CI) 5.3-39) in those patients. Peripheral blood cells gene expression of myocardin, an early myocardial marker, may serve as prognostic biomarkers of the long-term outcome of patients with NIDCM. Our findings open new prospects in the risk stratification of these patients.

Peripheral Blood MicroRNAs as Potential Biomarkers of Myocardial Damage in Acute Viral Myocarditis.

BACKGROUND: microRNAs (miRs) have emerged as important modulators of cardiovascular development and disease. Our aim was to determine whether cardiac-related miRs such as miR-21-5p and miR-1-3p were differentially expressed in acute viral myocarditis and whether any of them was related with the extent of myocardial damage and left ventricular dysfunction. METHODS: We enrolled 40 patients with acute viral myocarditis. Blood samples were taken on admission and miRs expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. RESULTS: miR-21-5p, miR-1-3p were significantly elevated in acute myocarditis. miR-21-5p levels showed a strong correlation with global longitudinal strain (r = 0.71, p < 0.01), while miR-1-3p had significant correlations with troponin I (r = 0.79, p < 0.01). CONCLUSIONS: The expression of miR-21-5p and miR-1-3p in peripheral blood is increased in acute viral myocarditis, and this increase is correlated with myocardial damage and indicative of left ventricular systolic dysfunction in these patients.

The impact of paced QRS duration on the expression of genes related to contractile function of the left ventricle in chronically paced patients from the right ventricular apex.

BACKGROUND: Right ventricular (RV) apex has proven to induce abnormal left ventricular (LV) activation pattern leading to pacing-induced cardiomyopathy (PICM) in a substantial percentage of paced patients. This study assessed the impact of paced QRS duration on the expression in the peripheral blood of sarcoplasmic reticulum calcium ATPase (SERCA) and investigated whether its width is related to the extend of LV remodelling. METHODS: We enrolled 52 consecutive patients with preserved ejection fraction (EF) who underwent pacemaker implantation for bradycardic indications. Group A consisted of 24 patients paced for atrioventricular conduction disturbances with QRS = 142 ± 12 ms post-implant and group B of 28 patients paced for sinus node disease with QRS = 94 ± 2%ms post-implant. mRNA levels of SERCA were assesed at implantation, 3, 6 and 12 months follow-up, while echocardiographic parameters at implantation, 1, 2 and 4 years. RESULTS: In group A, mRNA levels of SERCA decreased significantly at 3 months and remained low at 6 and 12 months' follow-up and were associated to the deterioration of LV function and geometry. Paced QRS duration was associated to both the alteration in the expression of SERCA and to the extend of LV remodelling. In group B no statistically significant change was demonstrated. CONCLUSIONS: Permanent RV pacing in patients with preserved EF and wide QRS post-implant is associated with a significant reduction of mRNA levels of SERCA. Paced QRS duration is associated to alterations in the expression of SERCA which precede adverse LV remodelling.

Platelet microRNAs in hypertensive patients with and without cardiovascular disease.

Platelets contain abundant microRNAs (miRs) that regulate gene expression and protein synthesis and may reflect platelet activation. We assessed platelet levels of miR-223, miR-126, and miR-22 in 82 patients with essential hypertension and 28 healthy individuals, using real-time reverse transcription polymerase chain reaction, and evaluated their relation with the patients' clinical profile. Hypertensives had significantly lower platelet miR-22 and miR-223 levels (97.6 ± 170.3 in hypertensives versus 193.8 ± 228.9 in normotensives, p = 0.011, for miR-22; 91.3 ± 154.1 in hypertensives versus 189.9 ± 266.3 in normotensives, p = 0.022, for miR-223). Significant differences in platelet miR levels were also observed between hypertensives who had cardiovascular disease and those who did not (4.1 ± 3.6 versus 75.1 ± 85.2 for miR-126, 24.3 ± 62.9 versus 122.8 ± 187.9 for miR-22, and 10.1 ± 10.4 versus 119.3 ± 169.0 for miR-223, respectively; p < 0.001 for all). In addition, we found a significant negative correlation with systolic blood pressure (SBP) (r = -0.43, p < 0.001, for miR-22; r = -0.47, p < 0.001, for miR-223 in hypertensives; and r = -0.54, p < 0.001, for miR-126). Finally, receiver operating characteristic analysis showed that platelet miR levels were also strong prognostic markers for cardiovascular disease in these patients. In conclusion, platelet miR-22 and miR-223 levels are reduced according to the hypertension status and they are negatively correlated with SBP levels. Platelet miR levels are also related to the presence of overt cardiovascular disease in this population. Further studies are needed to elucidate the exact role of platelet miRs in platelet function and their utility as novel biomarkers of atherothrombotic risk in those patients.

The long non-coding RNAs MHRT, FENDRR and CARMEN, their expression levels in peripheral blood mononuclear cells in patients with essential hypertension and their relation to heart hypertrophy.

Long non-coding RNAs (lncRNAs) participate in the modulation of cardiac hypertrophy, and they represent potential therapeutic targets in cardiovascular disease. We investigated the expression profiles of selected lncRNAs in peripheral blood mononuclear cells of patients with essential hypertension in relation to left ventricular hypertrophy. We assessed the expression levels of the lncRNAs MHRT, FENDRR and CARMEN using real-time reverse transcription polymerase chain reaction. Hypertensive patients showed significantly higher MHRT, FENDRR and CARMEN expression levels compared with healthy controls. In addition, we observed significant negative correlations of MHRT (r = -0.323, P = 0.003) and FENDRR (r = -0.380, P = 0.001) and a positive correlation of CARMEN (r = 0.458, P < 0.001) expression levels with left ventricular mass index. Our data reveal that the lncRNAs MHRT, FENDRR and CARMEN show distinct expression profiles in hypertensive patients and they possibly represent candidate therapeutic targets in hypertensive heart disease.

MicroRNAs in Peripheral Mononuclear Cells as Potential Biomarkers in Hypertensive Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: MicroRNAs (miRs) regulate gene expression and play an important role in ventricular and vascular remodeling. However, there are limited data regarding their role in heart failure with preserved ejection fraction (HFpEF). The aim of this study was to assess gene expression of miR-1, miR-133a, miR-21, miR-208b, miR-499, and miR-26b in peripheral blood mononuclear cells (PBMCs) in hypertensive patients with HFpEF and to evaluate their association with their exercise capacity. METHODS: We included 56 hypertensive patients with HFpEF (age 67.29 ± 7.75 years). Forty-two hypertensive patients without HFpEF (age 66.83 ± 7.17 years) served as controls. All subjects underwent a cardiopulmonary exercise test (CPXT). PBMCs were isolated and levels of miRs were determined by quantitative real-time reverse transcription polymerase chain reaction. RESULTS: For hypertensive patients with HFpEF, higher expression levels in PBMCs were found only for miR-26b (7.6 ± 7.3 vs. 4.0 ± 3.6, P = 0.002), miR-208b (28.8 ± 35.3 vs. 7.5 ± 13.3, P < 0.001), and miR-499 (14.2 ± 22.4 versus 3.5 ± 2.9, P = 0.001). The strongest correlations with CPXT parameters were found for miR-208b levels, which had a positive correlation with maximal oxygen uptake (peakVO2) (r = 0.671, P < 0.001), exercise duration (r = 0.445, P = 0.001), and minute ventilation-carbon dioxide production relationship (VE/VCO2) (r = 0.437, P = 0.001) in the HFpEF group. CONCLUSIONS: miR-26b, miR-208b, and miR-499 show a distinct in profile in hypertensive patients with HFpEF that is related with functional capacity. Further studies are needed to assess the role of miRs as prognostic tools or as therapeutic targets in those patients.

Bradykinin receptors gene expression in white adipose tissue in nondiabetic patients with coronary artery disease.

OBJECTIVES: Adipose tissue plays a key role in cardiovascular physiology. Kinin receptors are important determinant of the effect of adiposity on endothelial function and cardiovascular function. We examined the gene expression levels of kinin receptors in the subcutaneous white adipose tissue (sWAT) of nondiabetic patients with and without coronary artery disease (CAD). PATIENTS AND METHODS: We evaluated 21 patients with CAD (13 men, age: 68±8 years) and 23 patients without CAD (15 men, age: 66±5 years) who underwent catheterization through the femoral route. sWAT biopsies were obtained from the site of vessel puncture before the procedure and analyzed for bradykinin receptor type 1 (BKR1) and 2 (BKR2) gene expression by real-time quantitative PCR. RESULTS: Although BKR2 expression levels did not differ significantly (413.12±532.41 in CAD patients vs. 378.33±534.45 in controls, P=NS), BKR1 expression in sWAT was significantly greater in patients with CAD (352.69±455.12 vs. 46.5±46.7, P<0.05). Notably, BKR1 gene expression levels showed a significant positive correlation with BMI (r=0.45, P<0.002) and total cholesterol levels (r=0.53, P<0.001), and a negative correlation with fasting blood glucose (r=-0.4, P=0.006). CONCLUSION: There is a divergence in BKR1 gene expression in sWAT between patients with and without CAD and is associated with metabolic parameters. More studies are needed to determine the pathophysiological role of BKRs in adipogenesis, fat expansion, and atheromatous disease.

Increased platelet alpha2B-adrenergic receptor gene expression in well-controlled hypertensives: the effect of arterial stiffness.

Catecholamines play a major role in atherothrombotic mechanisms in essential hypertension. Alpha2B-adrenergic receptors (α2B-ARs) are implicated in the pathophysiology of platelet aggregation. In this study, we evaluated platelet α2B-AR gene expression levels in patients with well-controlled essential hypertension compared with normal individuals and investigated their association with increased arterial stiffness. Fifty-nine patients with well-controlled essential hypertension (34 men, mean age 65 ± 9 years) and 26 normotensives (19 men, mean age 64 ± 8 years) were included in the study. For each patient, carotid-femoral pulse wave velocity (PWV) and carotid-radial PWV were evaluated. In addition, blood samples were obtained and platelets were isolated. The α2B-AR gene expression levels in platelets were examined by real-time polymerase chain reaction for each participant. Well-controlled hypertensive patients showed significantly higher gene expression levels of α2B-Rs in platelets compared with normotensives (34.7 ± 29.5 vs 17.6 ± 12.5, respectively, P = .005). Interestingly, we found that carotid-femoral PWV and carotid-radial PWV were positively correlated with platelet α2B-R gene expression levels (r = 0.59, P < .001, and r = 0.39, P = .002, respectively).Platelet α2B-R gene expression levels are increased in patients with well-controlled essential hypertension compared with normotensives and are correlated with increased PWV in those patients. Our data indicate an association of arterial stiffness and platelet α2B-Rs gene expression and indicate the need for further research.

Low Levels of MicroRNA-21 Are a Marker of Reduced Arterial Stiffness in Well-Controlled Hypertension.

MicroRNAs (miRNAs) play a crucial role in myocardial and vascular remodeling and have emerged as potential diagnostic and prognostic biomarkers or as therapeutic targets. The authors aimed to investigate the expression profile of selected miRNAs in the peripheral blood of patients with well-controlled essential hypertension in relation to arterial stiffness. Expression levels of miRNAs miRNA-1, miRNA-133a, miRNA-26b, miRNA-208b, miRNA-499, and miRNA-21 in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Carotid-femoral pulse wave velocity (cfPWV) and carotid radial pulse wave velocity (crPWV) were evaluated at baseline and after 1 year of effective antihypertensive therapy. A total of 95 patients (50 men, mean age 62±9 years) with well-controlled essential hypertension were included in the analysis. Only miRNA-21 was independently correlated with changes in both cfPWV and crPWV, independently of blood pressure levels (r=-0.56 and r=-0.46, respectively; P<.001 for both). Low levels of miRNA-21 are strongly associated with an improvement in arterial stiffness in patients with well-controlled essential hypertension, independently of their blood pressure levels. These data highlight the significance of miRNA-21 in vascular remodeling and its role as a potential prognostic marker and future therapeutic target.

Endothelial progenitor cells as markers of severity in hypertrophic cardiomyopathy.

AIMS: Endothelial progenitor cells (EPCs) are bone marrow-derived cells that are mobilized into the circulation to migrate and differentiate into mature endothelial cells contributing to post-natal physiological and pathological neovascularization. In this study, we evaluated circulating EPCs in patients with hypertrophic cardiomyopathy (HCM) and examined a potential association with clinical parameters of the disease. METHODS AND RESULTS: We included 40 HCM patients and 23 healthy individuals. Using flow cytometry we measured EPCs in peripheral blood as two subpopulations of CD45-/CD34+/VEGFR2+ and CD45-/CD34+/CD133+ cells. Circulating CD45-/CD34+/VEGFR2+ cells were significantly increased in HCM patients in comparison with the controls (0.000238 ± 0.0003136 vs. 0.000057 ± 0.0001316, respectively, P = 0.002). However, there was no significant difference in the number of circulating CD45-/CD34+/CD133+ cells (0.003079 ± 0.0033288 vs. 0.002065 ± 0.0022173, respectively, P = 0.153). The CD45-/CD34+/VEGFR2+ subpopulation revealed a moderate correlation with LV mass index (r = 0.35, P = 0.026), while both EPC subpopulation levels showed strong positive correlations with th E/e' ratio (r = 0.423, P = 0.007 for CD45-/CD34+/VEGFR2+ and r = 0.572, P < 0.001 for CD45-/CD34+/CD133+). CONCLUSION: HCM patients showed an increased mobilization of EPCs compared with healthy individuals that correlated with diastolic dysfunction. Our findings may open up new dimensions in the pathophysiology, prognostication, and treatment of HCM.

Hypertrophic and antihypertrophic microRNA levels in peripheral blood mononuclear cells and their relationship to left ventricular hypertrophy in patients with essential hypertension.

MicroRNAs regulate several aspects of physiological and pathologic cardiac hypertrophy, and they represent promising therapeutic targets in cardiovascular disease. We assessed the expression levels of the microRNAs miR-1, miR-133a, miR-26b, miR-208b, miR-499, and miR-21, in 102 patients with essential hypertension and 30 healthy individuals. All patients underwent two-dimensional echocardiography. MicroRNA expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Hypertensive patients showed significantly lower miR-133a (5.06 ± 0.50 vs. 13.20 ± 2.15, P < .001) and miR-26b (6.76 ± 0.53 vs. 9.36 ± 1.40, P = .037) and higher miR-1 (25.99 ± 3.07 vs. 12.28 ± 2.06, P = .019), miR-208b (22.29 ± 2.96 vs. 8.73 ± 1.59, P = .016), miR-499 (10.06 ± 1.05 vs. 5.70 ± 0.91, P = .033), and miR-21 (2.75 ± 0.15 vs. 1.82 ± 0.20, P = .002) expression levels compared with healthy controls. In hypertensive patients, we observed significant negative correlations of miR-1 (r = -0.374, P < .001) and miR-133a (r = -0.431, P < .001) and significant positive correlations of miR-26b (r = 0.302, P = .002), miR-208b (r = 0.426, P < .001), miR-499 (r = 0.433, P < .001) and miR-21 (r = 0.498, P < .001) expression levels with left ventricular mass index. Our data reveal that miR-1, miR-133a, miR-26b, miR-208b, miR-499, and miR-21 show distinct expression profiles in hypertensive patients relative to healthy individuals and they are associated with clinical indices of left ventricular hypertrophy in hypertensive patients. Thus, they may be related to heart hypertrophy in hypertensive patients and are possibly candidate therapeutic targets in hypertensive heart disease.

Alterations in the expression of genes related to contractile function and hypertrophy of the left ventricle in chronically paced patients from the right ventricular apex.

AIM: Long-term right ventricular apical (RVA) pacing may lead to left ventricular (LV) remodelling and heart failure. This study assessed changes in the expression of genes regulating LV contractile function and hypertrophy, after permanent RVA pacing and investigated whether such changes proceed or even predict LV remodelling. METHODS AND RESULTS: We enrolled 52 consecutive patients (age 79.1 ± 7.7 years, 34 males) who underwent pacemaker implantation for bradycardic indications: Group A, 24 individuals with atrioventricular conduction disturbances and group B, 28 patients with sinus node disease. In group A, peripheral blood mRNA levels of gene sarcoplasmic reticulum calcium ATPase decreased at 3, 6, and 12 months' follow-up, while α-myosin heavy chain (MHC) decreased and ß-MHC increased until 6 months follow-up. In this group, 25% of patients demonstrated significant LV remodelling. At 4 years, LV end-systolic diameter increased from 29.67 ± 3.39 mm at baseline to 35.38 ± 4.22 mm, LV end-diastolic diameter increased from 50 ± 4.95 to 56.71 ± 5.52 mm, and ejection fraction declined from 63.04 ± 10.22 to 52.83 ± 10.81%. Early alterations in gene expression were associated with a deterioration in LV function and geometry that became apparent months later. In group B, echocardiographic indexes and mRNA levels of the evaluated genes demonstrated no statistically significant changes. CONCLUSIONS: Permanent RVA pacing in patients with preserved ejection fraction is associated with alterations in the expression of genes regulating LV contractile function and hypertrophy, measured in the peripheral blood. These alterations are traceable at an early stage, before echocardiographic changes are apparent and are associated with LV remodelling that becomes evident in the long term.

Circulating mesenchymal stem cells in patients with hypertrophic cardiomyopathy.

BACKGROUND: This study examines the mobilization of mesenchymal stem cells (MSCs) in patients with hypertrophic cardiomyopathy (HCM) compared to healthy individuals. The pathogenesis of myocardial hypertrophy in HCM is not fully understood. MSCs are involved in the process of neovascularization, fibrosis, and ventricular wall remodeling. METHODS AND RESULTS: We included 40 patients with HCM and 23 healthy individuals. Using flow cytometry, we measured MSCs in peripheral blood, as a population of CD45-/CD34-/CD90+ cells and also as a population of CD45-/CD34-/CD105+ cells. The resulting MSC counts were expressed as percentages of the total cells. Patients with HCM were found to have a greater percentage of circulating CD45-/CD34-CD34-/CD90+ cells compared to controls (0.0041±0.005% vs. 0.0007±0.001%, respectively, P<.001). No significant difference in circulating CD45-/CD34-/CD105+ cells in the peripheral blood was found between HCM patients and controls (0.016±0.018% vs. 0.012±0.014%, respectively, P=.4). Notably, circulating CD45-/CD34-/CD90+ cells were positively correlated with left ventricular mass index (r=0.54, P<.001). CONCLUSIONS: Patients with HCM reveal an increased mobilization of MSCs compared to healthy individuals. Although further research is needed to reveal the clinical significance of our findings, our data open a new dimension in the pathophysiology of the disease and may indicate new future therapeutic possibilities.

Increased mobilization of mesenchymal stem cells in patients with essential hypertension: the effect of left ventricular hypertrophy.

Stem cells have great clinical significance in many cardiovascular diseases. However, there are limited data regarding the involvement of mesenchymal stem cells (MSCs) in the pathophysiology of arterial hypertension. The aim of this study was to investigate the circulation of MSCs in patients with essential hypertension. The authors included 24 patients with untreated essential hypertension and 19 healthy individuals. Using flow cytometry, MSCs in peripheral blood, as a population of CD45-/CD34-/CD90+ cells and also as a population of CD45-/CD34-/CD105+ cells, were measured. The resulting counts were translated into the percentage of MSCs in the total cells. Hypertensive patients were shown to have increased circulating CD45-/CD34-/CD90+ compared with controls (0.0069%±0.012% compared with 0.00085%±0.0015%, respectively; P=.039). No significant difference in circulating CD45-/CD34-/CD105+ cells was found between hypertensive patients' and normotensive patients' peripheral blood (0.018%±0.013% compared with 0.015%±0.014%, respectively; P=.53). Notably, CD45-/CD34-/CD90+ circulating cells were positively correlated with left ventricular mass index (LVMI) (r=0.516, P<.001). Patients with essential hypertension have increased circulating MSCs compared with normotensive patients, and the number of MSCs is correlated with LVMI. These findings contribute to the understanding of the pathophysiology of hypertension and might suggest a future therapeutic target.

MicroRNA-9 and microRNA-126 expression levels in patients with essential hypertension: potential markers of target-organ damage.

MicroRNAs (miRs), as essential gene expression regulators, modulate cardiovascular development and disease and thus they are emerging as potential biomarkers and therapeutic targets in cardiovascular disease, including hypertension. We assessed the expression levels of the microRNAs miR-9 and miR-126 in 60 patients with untreated essential hypertension and 29 healthy individuals. All patients underwent two-dimensional echocardiography and 24-hour ambulatory blood pressure monitoring. MicroRNA expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Hypertensive patients showed significantly lower miR-9 (9.69 ± 1.56 vs 41.08 ± 6.06; P < .001) and miR-126 (3.88 ± 0.47 vs 8.96 ± 1.69; P < .001) expression levels compared with healthy controls. In hypertensive patients, miR-9 expression levels showed a significant positive correlation (r = 0.437; P < .001) with left ventricular mass index. Furthermore, both miR-9 (r = 0.312; P = .015) and miR-126 (r = 0.441; P < .001) expression levels in hypertensive patients showed significant positive correlations with the 24-hour mean pulse pressure. Our data reveal that miR-9 and miR-126 are closely related to essential hypertension in humans, as they show a distinct expression profile in hypertensive patients relative to healthy individuals, and they are associated with clinical prognostic indices of hypertensive target-organ damage in hypertensive patients. Thus, they may possibly represent potential biomarkers and candidate therapeutic targets in essential hypertension.