***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Purpose : Angiotensin-(1 - 7 ) [ Ang-(1 - 7 ) ] is an endogenous peptide hormone of the renin-angiotensin system with antiproliferative and antiangiogenic properties . The primary objective of this study was to establish the recommended phase II dose of Ang-(1 - 7 ) for treating patients with advanced cancer . Secondary objectives were to assess toxicities , pharmacokinetics , clinical activity , and plasma biomarkers . Experimental Design : Patients with advanced solid tumors refractory to st and ard therapy were treated with escalating doses of Ang-(1 - 7 ) in cohorts of three patients .  Ang-(1 - 7 ) was administered by s.c . injection once daily for 5 days on a 3-week cycle . Tumor measurements were done every two cycles and treatment was continued until disease progression or unacceptable toxicity . Results : Eighteen patients were enrolled . Dose-limiting toxicities encountered at the 700 μg/kg dose included stroke ( grade 4 ) and reversible cranial neuropathy ( grade 3 ) . Other toxicities were generally mild . One patient developed a 19 % reduction in tumor measurements . Three additional patients showed clinical benefit with stabilization of disease lasting more than 3 months . On day 1 , Ang-(1 - 7 ) administration led to a decrease in plasma placental growth factor ( PlGF ) levels in patients with clinical benefit ( P = 0.04 ) but not in patients without clinical benefit ( P = 0.25 ) . On day 5 , PlGF levels remained lower in patients with clinical benefit compared with patients without clinical benefit ( P = 0.04 ) . Conclusions : Ang-(1 - 7 ) is a first-in-class antiangiogenic drug with activity for treating cancer that is linked to reduction of plasma PlGF levels . The recommended phase II dose is 400 μg/kg for this administration schedule . ( Clin Cancer Res 2009;15(23):7398–404 Purpose : Multilineage cytopenias occur following myelosuppressive chemotherapy . Most hematopoietic agents differentiate along a single lineage and fail to prevent progressive cytopenias . Angiotensin 1 - 7 [ A(1 - 7 ) ] is a hematopoietic agent that stimulates the proliferation of multipotential and differentiated progenitor cells in cultured bone marrow and human cord blood . The purpose of this study was to determine the optimal biologic dose and the maximum tolerated dose of A(1 - 7 ) . Experimental design : This study determined the safety and activity of A(1 - 7 ) following chemotherapy in patients with breast cancer .  Toxicity was assessed by administering A(1 - 7 ) daily for 7 days followed by a 7-day washout prior to the first cycle of chemotherapy . Beginning 2 days after chemotherapy and continuing daily for at least 10 days , fifteen patients received five different A(1 - 7 ) doses and five patients received filgrastim as a comparator group over three cycles of chemotherapy . Results : No dose-limiting toxicity was observed following A(1 - 7 ) . The frequency of adverse events was slightly lower in A(1 - 7 ) than in filgrastim patients . No patient required a chemotherapy modification due to hematologic toxicity . There was an apparent differential dose-response sensitivity of the various lineages to A(1 - 7 ) . At a dose of 100 μg/kg , A(1 - 7 ) reduced the frequency of grade 2–4 thrombocytopenia , anemia , and grade 3–4 lymphopenia as compared to filgrastim . Conclusion : These data suggest that A(1 - 7 ) may be beneficial in attenuating multilineage cytopenias following chemotherapy at a dose of 100 μg/kg per day Abstract —Previous animal studies have shown that angiotensin (Ang)-(1 - 7 ) is a biologically active component of the renin-angiotensin system , acting as a vasoactive agent , and may play a role in the blood pressure regulation . There is little information , however , on the effect of Ang-(1 - 7 ) on human circulation or the mechanism of its action . To investigate the effect of Ang-(1 - 7 ) on forearm circulation and to determine whether this effect is altered in patients with essential hypertension , we measured change in forearm blood flow using venous occlusion plethysmography in response to intra-arterial infusion of Ang-(1 - 7 ) ( 10−10 , 10−9 , and 10−8 mol/min ; for 5 minutes ) in normotensive control subjects ( n=8 ) and patients with essential hypertension ( n=8 ) . Infusion of Ang-(1 - 7 ) significantly increased the forearm blood flow response in a dose-dependent manner in both normotensive control subjects ( 28.7±9.7 % , at 10−8 mol/min;P < 0.05 ) and hypertensive patients ( 31.8±15.2 % , at 10−8 mol/min;P < 0.05 ) . The vasodilatory effect of Ang-(1 - 7 ) was similar in the two groups . Intra-arterial infusion of NG-monomethyl-l-arginine , a nitric oxide synthesis inhibitor , did not alter the forearm blood flow response to Ang-(1 - 7 ) in either group . These findings suggest that Ang-(1 - 7 ) causes vasodilation in forearm circulation of normotensive subjects and patients with essential hypertension through a pathway that is independent of nitric oxide synthesis Abstract — Studies in isolated vessels and rat models of hypertension suggest that angiotensin (Ang)-(1 - 7 ) potentiates the vasodilator effect of bradykinin , possibly through ACE inhibition . We therefore tested the hypothesis that Ang-(1 - 7 ) potentiates the vasodilator or tissue plasminogen activator ( TPA ) response to bradykinin in the human forearm vasculature . Grade d doses of Ang-(1 - 7 ) ( 10 , 100 , and 300 pmol/min ) , bradykinin ( 47 , 94 , and 189 pmol/min ) , and Ang I ( 1 , 10 , and 30 pmol/min ) were administered through the brachial artery to 8 normotensive subjects in r and om order . Thirty minutes after initiation of a constant infusion of Ang-(1 - 7 ) ( 100 pmol/min ) , bradykinin and Ang I infusions were repeated . There were no systemic hemodynamic effects of the agonists . Bradykinin significantly increased forearm blood flow ( P < 0.001 , from 3.8±0.5 to 13.9±3.1 mL/min per 100 mL at 189 pmol/min ) and net TPA release ( P = 0.007 , from 1.1±1.0 to 23.6±6.2 ng/min per 100 mL at 189 pmol/min ) , whereas Ang I caused vasoconstriction ( P = 0.003 , from 3.3±0.4 to 2.5±0.3 mL/min per 100 mL at 30-pmol/min dose ) . There was no effect of Ang-(1 - 7 ) on either forearm blood flow ( P = 0.62 , 3.3±0.4 to 3.5±0.4 mL/min per 100 mL at 300 pmol/min ) or TPA release ( P = 0.52 , from 0.7±0.8 to 1.0±0.7 ng/min/100 mL at 300 pmol/min ) . Moreover , there was no effect of 100 pmol/min Ang-(1 - 7 ) on the vasodilator [ P = 0.46 for Ang-(1 - 7 ) effect ] or TPA [ P = 0.82 for Ang-(1 - 7 ) effect ] response to bradykinin or the vasoconstrictor response to Ang I [ P = 0.62 for Ang-(1 - 7 ) effect ] . These data do not support a role of Ang-(1 - 7 ) , given at supraphysiological doses , in the regulation of human peripheral vascular resistance or fibrinolysis Angiotensin-(1 - 7 ) is a product of angiotensin processing that has been proposed to have vasodepressor effects , both on its own and in combination with bradykinin , which may be pathophysiologically and therapeutically important . Despite this , there has been very little examination of its effects in humans and none in heart failure patients or in other patients treated with ACE inhibitors . We therefore sought to determine the effects of angiotensin-(1 - 7 ) in patients with heart failure treated with an ACE inhibitor  , as well as any interaction with the effects of bradykinin . A locally active dose of angiotensin-(1 - 7 ) , alone and in combination with bradykinin , was infused into the nondominant brachial artery while forearm blood flow was measured by venous occlusion plethysmography in 8 patients with heart failure treated with ACE inhibitors .  Although bradykinin on its own caused profound vasodilation , there was no effect of angiotensin-(1 to 7 ) on its own or any effect of angiotensin-(1 - 7 ) on the response to bradykinin . We conclude that angiotensin-(1 - 7 ) is biologically inactive in the forearm circulation of patients with heart failure treated with an ACE inhibitor .  The contrast between these findings and previously reported pre clinical findings calls into question the relevance of angiotensin-(1 - 7 ) to the hemodynamic effects of ACE inhibitors BACKGROUND Cardiac resynchronization reduces symptoms and improves left ventricular function in many patients with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony . We evaluated its effects on morbidity and mortality . METHODS Patients with New York Heart Association class III or IV heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony who were receiving st and ard pharmacologic therapy  were r and omly assigned to receive medical therapy alone or with cardiac resynchronization . The primary end point was the time to death from any cause or an unplanned hospitalization for a major cardiovascular event . The principal secondary end point was death from any cause . RESULTS A total of 813 patients were enrolled and followed for a mean of 29.4 months . The primary end point was reached by 159 patients in the cardiac-resynchronization group , as compared with 224 patients in the medical-therapy group ( 39 percent vs. 55 percent ; hazard ratio , 0.63 ; 95 percent confidence interval , 0.51 to 0.77 ; P<0.001 ) . There were 82 deaths in the cardiac-resynchronization group , as compared with 120 in the medical-therapy group ( 20 percent vs. 30 percent ; hazard ratio 0.64 ; 95 percent confidence interval , 0.48 to 0.85 ; P<0.002 ) . As compared with medical therapy , cardiac resynchronization reduced the interventricular mechanical delay , the end-systolic volume index , and the area of the mitral regurgitant jet ; increased the left ventricular ejection fraction ; and improved symptoms and the quality of life ( P<0.01 for all comparisons ) . CONCLUSIONS In patients with heart failure and cardiac dyssynchrony , cardiac resynchronization improves symptoms and the quality of life and reduces complications and the risk of death . These benefits are in addition to those afforded by st and ard pharmacologic therapy . The implantation of a cardiac-resynchronization device should routinely be considered in such patients Background It has been clearly demonstrated that angiotensin(1–7 ) potentiates the vasodilating effect of bradykinin in isolated vessels of animals . Objective To investigate the interaction between angiotensin(1–7 ) Ang(1–7 ) and bradykinin in human forearm resistant vessels of normotensive healthy men in vivo , by the measurement of forearm blood flow using venous occlusion , strain-gauge plethysmography with intra-arterial infusions of peptides in a placebo-controlled , double-blind , cross-over design . Methods In eight men , bradykinin was infused intra-arterially twice ; placebo , Ang(1–7 ) , or angiotensin II was co-infused with the second infusion . The effect of inhibition of nitric oxide synthase on the interaction between Ang(1–7 ) and bradykinin was also tested in eight other individuals . The effects of Ang(1–7 ) were analyzed by analysis of variance ( ANOVA ) and by the ratios of individually derived areas under the dose – response curves ( AUC ) of bradykinin , adjusted for changes in the AUCs by repeated infusions of bradykinin with placebo . Results Ang(1–7 ) ( 1000 pmol/min ) significantly potentiated the vasodilating effect of bradykinin compared with the effect of saline ( P = 0.0471 , ANOVA ) and in a dose-dependent manner ( adjusted AUC ratio [ 95 % confidence interval ( CI ) ] 2.75 ( 1.72 to 3.78 ) with 1000 pmol/min , 1.62 ( 1.31 to 1.93 ) with 100 pmol/min , and 0.98 ( 0.80 , to 1.09 ) with 10 pmol/min ) . This effect was completely abolished by co-infusion of NG-monomethyl-l-arginine [ AUC ratio 0.98 ( 
    Output:
    
Cardioprotective effects seen in non-HF studies include for instance beneficial actions against atherosclerosis and myocardial fibrosis .
The main finding of our systematic review is that Angiotensin-(1 - 7 ) plays an important cardioprotective role in HF in animals and in patients without heart failure .