Egidio Imbalzano

Pulse wave velocity and augmentation index, but not intima-media thickness, are early indicators of vascular damage in hypercholesterolemic children

Eur J Clin Invest 2010; 40 (3): 250–257

Smoke exposure and circulating progenitor cells: Evidence for modulation of antioxidant enzymes and cell count

BACKGROUND Cigarette smoking is involved in vascular inflammation and impairment of circulating progenitor cells (CPCs), including endothelial progenitor cells (EPCs). The study aim was to evaluate the redox balance of these cells in relation to smoking exposure. METHODS Circulating cells from 36 healthy smokers and 26 controls were isolated and identified by flow cytometry. ROS generation, mRNA and protein cell expression, and enzymatic activity of MnSOD, catalase, and GPx-1 were evaluated. RESULTS Smokers showed higher levels of CRP and fibrinogen and lower levels of HDL-C. ROS and MnSOD were higher (p<0.001), while catalase and GPx-1 were lower (p<0.001) as was EPC number (p<0.001) in smokers. CPC and EPC correlated with HDL-C, CRP, ROS and enzyme expression and activity. CONCLUSIONS Our data suggest that smoking exposure involves antioxidant enzymes in CPCs and EPCs and that the inflammatory response in smokers plays an important role in impairing cells and their antioxidant functions.

Circulating progenitor cells are increased in newly diagnosed untreated hypertensive patients with arterial stiffening but normal carotid intima-media thickness

Circulating progenitor cells (CPCs), including endothelial progenitor cells (EPCs), have a key role in endothelium repair. Cellular NADPH oxidase (Nox) enzymes, including Nox-containing gp91phox, represent a source of reactive oxygen species (ROS); ROS trigger protective signals but may also have detrimental effects. Cellular defenses against ROS include the enzymes manganese superoxide dismutase (MnSOD), catalase (CAT) and glutathione peroxidase type-1 (GPx-1). We investigated the relationships of CPCs with cellular gp91phox, MnSOD, CAT, GPx-1 and ROS levels and with carotid intima-media thickness (cIMT) and stiffness in hypertensives without additional risk factors for cardiovascular disease. CPCs from 53 newly diagnosed, untreated hypertensives and from 29 controls were isolated and identified by flow cytometry. gp91phox, MnSOD, CAT, and GPx-1 mRNA and protein expression and ROS generation were evaluated in enriched samples of CD34+ cells; cIMT and stiffness were assessed. Hypertensives showed higher arterial stiffness (P<0.001) but no difference in cIMT with respect to controls. ROS generation was slightly increased (P=0.04), whereas gp91phox, MnSOD, CAT and GPx-1 were significantly higher (P<0.001) with respect to controls, as was CPC number (P<0.001), but EPCs were no different. CPC and EPC numbers correlated with gp91phox, ROS and fibrinogen (P<0.001); moreover, gp91phox, MnSOD, CAT and GPx-1 were correlated with CPC number. In early phases of arterial hypertension, before the development of wall thickening and even in the presence of arterial mechanical impairment, CPC number may be increased to maintain an adequate number of EPCs in peripheral blood.

Biglycan expression in hypertensive subjects with normal or increased carotid intima-media wall thickness

BACKGROUND Biglycan (BGN), an extracellular matrix proteoglycan, has been shown to convey pro-inflammatory signals. In the present study we investigated BGN expression and its correlation with plasma levels of inflammatory markers in hypertensive subjects with or without alteration of carotid intima media thickness (IMT). METHODS We evaluated 123 untreated essential hypertensives with no additional risk factors for atherosclerosis nor signs of cardiovascular disease and 40 controls. Hypertensives were classified according to a normal (< or =1 mm) or increased (>1 mm) IMT. BGN-mRNA and protein expression were measured in unstimulated, LPS- and Angiotensin II (Ang-II)-stimulated blood monocytes. Plasma concentrations of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and high sensitivity-C-reactive protein (hs-CRP) were also measured. RESULTS We found increased levels of IL-6, TNF-alpha, hs-CRP, and BGN-mRNA and protein in hypertensives vs controls (1.72+/-0.60 vs 1 n-fold, and 3.60+/-0.75 vs 1 n-fold, both p<0.001). However, BGN expression was not significantly different between hypertensives with IMT < or =1 mm and >1 mm. Furthermore, in vitro addition of Ang II enhanced basal BGN-mRNA (in hypertensives: 3.57+/-1.08 vs 1.72+/-0.60 n-fold, p<0.001) and protein (in hypertensives: 4.92+/-0.42 vs 3.41+/-0.75, p<0.001) expression in monocytes. CONCLUSIONS Our data provide evidence of an enhanced expression of BGN in essential hypertension. In addition we suggest that Ang II can mediate monocyte BGN production.

The chance finding at multislice computed tomography coronary angiography of an ectopic origin of the left circumflex coronary artery from the right sinus of Valsalva

Anomalous coronary arteries occur in less than 2% of the general population. Most coronary anomalies are clinically asymptomatic. However some of them may present with chest pain, syncope, heart failure and sudden death. Acute myocardial infarction has been also described. Extravascular coronary compression results in dynamic obstruction which can cause effort angina as well as syncope and anomalous coronary arteries with an inter-arterial course are associated with sudden cardiac death. Anomalous origin of the circumflex coronary artery from the right sinus of Valsalva is thought to be of little clinical significance without the presence of severe narrowing of the vessel. Adequate visualization of the anomaly is essential for proper patient management. It has reported the full capability and accuracy of computed tomography coronary angiography in the identification and evaluation of the ectopic origin of the left circumflex coronary artery from the right sinus of Valsalva, displaying accurately the origin, size, course, and relationship of the anomalous vessel with respect to surrounding structures. We report a case of chance finding at multislice computed tomography coronary angiography of an ectopic origin of the left circumflex coronary artery from the right sinus of Valsalva. Also this case focuses attention on the anomalous origin of the circumflex coronary artery from the right sinus of Valsalva and confirms the full capability and accuracy of computed tomography coronary angiography in its adequate visualization.

Clinical variants in Ebstein's anomaly

Exbsteins anomaly (EA) is a rare congenital cardiac malformation, which is associated with morphological and electrophysiological abnormalities [1–21]. The incidence is assessed b 1% but it is often underdiagnosed because of the existence of minor forms, sometimes difficult to recognize [22–24]. EA is defined as the significant apical displacement of the septal tricuspid valve leaflet and the presence of a redundant, elongated, anterior tricuspid valve leaflet, causing a significant regurgitation, associated with a reduction of the functional right ventricle, right atrial and right ventricular dilatation and supraventricular and ventricular arrhythmias [1–25]. Generally EA is diagnosed in pediatric age or during the pregnancy but often the first diagnosis is made in the adult [26,27]. We made a case report about a patient of 62 years, who underwent for a cardiologic physical exam for moderate labour dyspnoea. The ECG showed atrial fibrillation. At the echocardiogram there were clear alterations involving the tricuspid valve and suggesting an EA (Fig. 1). This case shows that EA may present with various patterns, which may be at the base of numerous clinical manifestations between pediatric and adult age [28,29]. This variability derives from the different size of the tricuspid valve displacement, from the different size between the right “atrialized” ventricle and the remaining functional right ventricle, from the functionality of the tricuspid leaflets and from the presence of other heart congenital diseases [28–35]. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.

Left coronary artery fistula to right ventricle complicated heart failure in a patient on hemodialysis

Coronary artery fistulas (CAF) are rare, and are most often diagnosed by echocardiography or by coronary angiography. The incidence of this disease is very low, with a more frequent occurrence of fistulas originating in the right coronary artery. There is a higher incidence of CAF to right heart chambers, with CAF to the left ventricle (LV) being rare. Treatment can be surgical or percutaneous [1]. This report describes a case of CAF to the right ventricle (RV) resulting in severe pulmonary hypertension, in a patient with end-stage renal disease (ESRD) on hemodialysis and rheumatoid arthritis [2]. The patient had a history of hypertension for over 30 years [3]. Computed tomographic pulmonary angiography ruled out pulmonary embolism, but it suggested a coronary fistula to the RV cavity. A 61-year-old woman was referred for cardiac evaluation for chest pain and worsening dyspnea. The patient was on maintenance hemodialysis for the prior 2 years owing to ESRD. Clinical examination revealed tachycardia, crackles at both bases with no wheezes, rhonchi, or other adventitious sounds, a blood pressure of 160/70 mmHg. The patient had a radio-cephalic fistula constructed at the left wrist between the radial artery and the cephalic vein, using end-to-end anastomosis. An electrocardiogram showed evidence of a right bundle branch block, and signs of ventricular overload. Cross-sectional echocardiography with Doppler interrogation revealed a left ventricular ejection fraction of 55 %, and there was evidence of diastolic dysfunction, without important calcification or regurgitation of the valves.

Effects of the angiotensin II receptor blocker losartan on the monocyte expression of biglycan in hypertensive patients

1. Recently, we demonstrated that biglycan (BGN) is increased in circulating monocyte cells from hypertensive patients and that angiotensin (Ang) II is able to increase BGN expression. The present study was designed to investigate the effects of treatment with the angiotensin AT1 receptor antagonist losartan on monocyte BGN mRNA and protein expression in essential hypertension.

Endothelial Progenitor Cells for Diagnosis and Prognosis in Cardiovascular Disease.

Objective. To identify, evaluate, and synthesize evidence on the predictive power of circulating endothelial progenitor cells (EPCs) in cardiovascular disease, through a systematic review of quantitative studies. Data Sources. MEDLINE was searched using keywords related to “endothelial progenitor cells” and “endothelium” and, for the different categories, respectively, “smoking”; “blood pressure”; “diabetes mellitus” or “insulin resistance”; “dyslipidemia”; “aging” or “elderly”; “angina pectoris” or “myocardial infarction”; “stroke” or “cerebrovascular disease”; “homocysteine”; “C-reactive protein”; “vitamin D”. Study Selection. Database hits were evaluated against explicit inclusion criteria. From 927 database hits, 43 quantitative studies were included. Data Syntheses. EPC count has been suggested for cardiovascular risk estimation in the clinical practice, since it is currently accepted that EPCs can work as proangiogenic support cells, maintaining their importance as regenerative/reparative potential, and also as prognostic markers. Conclusions. EPCs showed an important role in identifying cardiovascular risk conditions, and to suggest their evaluation as predictor of outcomes appears to be reasonable in different defined clinical settings. Due to their capability of proliferation, circulation, and the development of functional progeny, great interest has been directed to therapeutic use of progenitor cells in atherosclerotic diseases. This trial is registered with registration number: Prospero CRD42015023717.

Vitamin D Status in Rheumatoid Arthritis: Inflammation, Arterial Stiffness and Circulating Progenitor Cell Number

Background and Aims Suboptimal vitamin D status was recently acknowledged as an independent predictor of cardiovascular diseases and all-cause mortality in several clinical settings, and its serum levels are commonly reduced in Rheumatoid Arthritis (RA). Patients affected by RA present accelerated atherosclerosis and increased cardiovascular morbidity and mortality with respect to the general population. In RA, it has been reported an impairment of the number and the activity of circulating proangiogenic haematopoietic cells (PHCs), including CD34+, that may play a role in endothelial homeostasis. The purpose of the study is to investigate the association between vitamin D levels and PHCs, inflammatory markers, and arterial stiffening in patients with RA. Methods and Results CD34+ cells were isolated from 27 RA patients and 41 controls. Vitamin D levels, C-reactive protein (CRP), fibrinogen, pulse wave velocity (PWV), and carotid intima-media thickness (cIMT) were also evaluated. CD34+ count and vitamin D levels were lower in RA patients as compared to controls, while fibrinogen, CRP, PWV and cIMT were higher in RA patients. CD34+ cell number appeared to be associated with vitamin D levels, and negatively correlated to fibrinogen and early atherosclerosis markers (PWV and cIMT); vitamin D levels appear also to be inversely associated to fibrinogen. Conclusions RA patients with moderate disease activity presented with low vitamin D levels, low CD34+ cell count, increased PWV and cIMT; we found that vitamin D deficiency is associated to CD34+ cell reduction in peripheral blood, and with fibrinogen levels. This suggests that vitamin D might contribute to endothelial homeostasis in patients with RA.