The profibrotic cytokine transforming growth factor-ß1 increases endothelial progenitor cell angiogenic properties.

BACKGROUND: Transforming growth factor-ß1 (TGF-ß1) is a profibrotic cytokine that plays a major role in vascular biology, and is known to regulate the phenotype and activity of various vascular cell populations. Because most fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF), are associated with vascular remodeling, and as endothelial progenitor cells (EPCs) may be involved in this process, we investigated the impact of TGF-ß1 modulation of EPC angiogenic properties. METHODS: TGF-ß1 plasma levels were determined in 64 patients with IPF and compared with those in controls. The effect of TGF-ß1 on angiogenesis was studied in vivo in a Matrigel plug model and in vitro on endothelial colony-forming cells (ECFCs). We studied the effects of inhibiting the expression of the three main receptors of TGF-ß1 in ECFCs by using short interfering RNA. RESULTS: Total TGF-ß1 plasma levels were significantly increased in patients with IPF as compared with controls (P < 0.0001). TGF-ß1 had proangiogenic effects in vivo by increasing hemoglobin content and blood vessel formation in Matrigel plugs implanted in C57/Bl6 mice, and in vitro by enhancing ECFC viability and migration. The effects were abolished by silencing the three main TGF-ß1 receptors. CONCLUSIONS: TGF-ß1 is proangiogenic in vivo and induces ECFC angiogenic properties in vitro, suggesting that TGF-ß1 may play a role during vascular remodeling in fibrotic disease states via EPCs.

From treating complex coronary artery disease to promoting cardiovascular health: therapeutic transitions and challenges, 2010-2020.

Cardiovascular disease (CVD) has become the most common cause of mortality worldwide. Obesity, insufficient physical exercise, diabetes, and advancing age are major risk factors for developing cardiovascular disease that are currently increasing in prevalence. Nevertheless, significant progress has recently been made in the treatment of complex cardiovascular and coronary artery disease (CAD), with pharmacological management set to assume an increasingly important role. Other timely factors, such as the development of the polypill and high-level medical and political interest in advancing cardiovascular health, are driving forces that may help to make inroads into the global cardiovascular disease burden. In this article, we critically review the key challenges that we face in the coming decade as we strive to transition and apply our growing knowledge of complex CAD to promoting global cardiovascular health.

Update on the use of stem cells for cardiac disease.

Major advances have recently been made in our understanding of stem cell biology, and in the application of stem cells to treat cardiac disease. Resident cardiac stem cells have now been described and the long-accepted paradigm of the adult mammalian heart as an organ without regenerative capacity has been questioned. Various stem-cell-based approaches for ameliorating cardiac disease have been shown to be beneficial in animal models and are now being trialled in humans, with several phase I clinical studies already completed. Although these clinical studies lacked adequate placebo controls, they have consistently shown promising results. If confirmed by larger phase II/III trials, it is possible that within a few years a powerful new therapeutic option may be available for the burgeoning number of patients suffering from myocardial ischaemia and/or other cardiac disorders.

Percutaneous carotid artery stenting: a strategy in evolution.

BACKGROUND: Carotid stenting was initially proposed as an alternative to surgical endarterectomy for selected high-risk patients. More recently, patients of standard surgical risk are being considered for percutaneous treatment of their carotid disease. AIMS: To describe the clinical outcomes of an initial consecutive cohort of patients treated by carotid stenting at one institution. METHODS: Between December 1997 and July 2003, 111 patients underwent stenting of 118 carotid arteries. Peri-procedural and long-term outcome data were collected. RESULTS: Most patients (>70%) were high-risk candidates for endarterectomy. Stents were successfully placed in 117/118 carotid arteries (99.2%). Distal protection devices were used in 43/118 (36.4%). The peri-procedural rate of death or disabling stroke was 3/118 (2.5%). Death or any stroke occurred in 11/118 (9.3%). However, only 7/118 (5.9%) procedures resulted in death or any persistent stroke (neurological deficit >1 week post-procedure). No myocardial infarction occurred. Median length of post-procedure hospitalization was 1 day. Long-term follow up was possible for 101 patients (91.0%) over a mean period of 27.1 months. The Kaplan-Meier estimate of survival free of ipsilateral stroke 36 and 66 months after carotid stenting was 77.0 +/- 9.5% and 68.2 +/- 15.1%, respectively. The estimated survival free of any stroke or stent failure was 70.9 +/- 10.7% and 60.7 +/- 17.4%, respectively. The majority of late deaths (7/11) were due to cardiac disease. CONCLUSION: We conclude that stenting of carotid stenoses is feasible, with a high procedural success rate and low complication rate. Carotid stenting should be considered the procedure of choice for high-risk patients.

Hypertrophic cardiomyopathy: state-of-the-art review, with focus on the management of outflow obstruction.

Significant advances in our understanding and management of hypertrophic cardiomyopathy have been made in the last decade, as the complex genetics and phenotype-genotype correlations that characterize the disease are gradually unravelled. The well-described clinical heterogeneity of hypertrophic cardiomyopathy is now understood to be based on profound genetic variability, with at least 10 genes and over 150 mutations implicated. Several new therapeutic tools have entered clinical practice. The implantable cardioverter-defibrillator is now strongly indicated in those at high risk of sudden arrhythmic death. Our ability to abort sudden death in this subgroup has placed added emphasis on risk stratification in newly diagnosed patients. New procedures have also been developed for the relief of outflow obstruction in patients with refractory symptoms and a significant subaortic outflow gradient. Although not as efficacious as the 'gold-standard' surgical myectomy-myotomy, dual-chamber pacemaker implantation can be of modest benefit in select patients. Percutaneous transluminal septal myocardial ablation is an emerging catheter-based procedure for the relief of left ventricular outflow obstruction. Long-term follow-up data are still awaited. However, intermediate-term results suggest equivalent efficacy to surgical myectomy-myotomy.

Resting whole blood viscosity of elite rowers is related to performance.

This study investigated the relationships between resting whole blood viscosity (WBV), haemoglobin concentration (HGB), haematocrit (HCT), and performance in 25 highly-trained national squad rowers (11 women and 14 men). The WBV and HGB were measured at rest prior to a 2500 m simulated race on a Concept rowing ergometer when performance (P) was measured by average velocity. A group of 12 rowers were measured on just one occasion, another 11 were measured twice with an intervening 5 weeks of continued training and 2 were measured three times, the third test after another 4 weeks. Regression analyses making simultaneous use of both intra- and interindividual data indicated a significant inverse relationship between P and WBV (at both high and low shear rates), a relationship which was strengthened after statistically controlling for the effects of HGB, this effect being slightly more significant than HCT. A significant positive regression also emerged between P and HGB, but only after statistically controlling for the influence of WBV at high shear rate. Overall, stronger relationships were demonstrated in the male rowers compared with the female. These data, in the light of previous evidence that fitter people tend to have lower WBV, would indicate that blood rheology unrelated to HGB (or HCT) is related to performance in relatively homogeneous and already highly-trained athletes.