Temporal Changes in Extracellular Vesicle Hemostatic Protein Composition Predict Favourable Left Ventricular Remodeling after Acute Myocardial Infarction.

The subset of plasma extracellular vesicles (EVs) that coprecipitate with low-density lipoprotein (LDL-EVs) carry coagulation and fibrinolysis pathway proteins as cargo. We investigated the association between LDL-EV hemostatic/fibrinolysis protein ratios and post-acute myocardial infarction (post-AMI) left ventricular (LV) remodeling which precedes heart failure. Protein concentrations of von Willebrand factor (VWF), SerpinC1 and plasminogen were determined in LDL-EVs extracted from plasma samples obtained at baseline (within 72 h post-AMI), 1 month and 6 months post-AMI from 198 patients.

Plasma tissue factor coagulation activity in post-acute myocardial infarction patients.

Introduction: Coagulation is involved in fibroproliferative responses following acute myocardial infarction (AMI). Left ventricular (LV) remodeling following AMI is closely associated with progression to heart failure. This study aims to assess the association between plasma tissue factor activity and LV remodeling in post-AMI patients.

Growth factors: avenues for the treatment of myocardial infarction and potential delivery strategies.

Acute myocardial infarction (AMI) is one of the leading causes of death worldwide. Despite recent advances in clinical management, reoccurence of heart failure after AMI remains high, in part because of the limited capacity of cardiac tissue to repair after AMI-induced cell death. Growth factor-based therapy has emerged as an alternative AMI treatment strategy.

The Functional Role of Lipoproteins in Atherosclerosis: Novel Directions for Diagnosis and Targeting Therapy.

Dyslipidemia, characterized by a high level of lipids (cholesterol, triglycerides, or both), can increase the risk of developing and progressing atherosclerosis. As atherosclerosis progresses, the number and severity of aterial plagues increases with greater risk of myocardial infarction, a major contributor to cardiovascular mortality. Atherosclerosis progresses in four phases, namely endothelial dysfunction, fatty streak formation, lesion progression and plaque rupture, and eventually thrombosis and arterial obstruction.

Skeletal contributions to plasma CNP forms: evidence from regional sampling in growing lambs.

Unlike the cardiac circulating hormones, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), C-type natriuretic peptide (CNP) appears to be largely tissue-based and circulates at concentrations considered insufficient to affect organ function. Consistent with CNP's crucial role in regulating skeletal growth, serial studies in juveniles show that both plasma CNP and aminoterminal proCNP (NTproCNP) are highly correlated with growth velocity raising the possibility that skeletal tissues contribute to circulating concentrations of CNP forms during the growing period. Hypothesizing that venous blood draining from bone dense regions is relatively enriched in CNP, we have performed trans-organ regional blood sampling for measurement of CNP forms in 4-week-old lambs and compared the findings to simultaneous levels of ANP and BNP.

Urocortin 1 administration from onset of rapid left ventricular pacing represses progression to overt heart failure.

Urocortin 1 (Ucn1) may be involved in the pathophysiology of heart failure (HF), but the impact of Ucn1 administration on progression of the disease is unknown. The aim of this study was to investigate the effects of Ucn1 in sheep from the onset of cardiac overload and during the subsequent development of HF. Eight sheep underwent two 4-day periods of HF induction by rapid left ventricular pacing (225 beats/min) in conjunction with continuous infusions of Ucn1 (0.

Urocortin 3: haemodynamic, hormonal, and renal effects in experimental heart failure.

Aims: To investigate the haemodynamic, hormonal, and renal effects of peripheral urocortin 3 (Ucn3) administration for the first time in either normal health or heart failure (HF).

Methods And Results: Eight sheep received incremental intravenous boli of Ucn3 (10, 50, and 100 microg at 2-h intervals) before (normal) and during pacing-induced HF. Compared with controls, Ucn3 induced immediate, dose-dependent increases in cardiac output (normal 4.

Four-day urocortin-I administration has sustained beneficial haemodynamic, hormonal, and renal effects in experimental heart failure.

Aims: To investigate the subacute effects of a sustained intravenous infusion of urocortin-I (Ucn-I) in experimental heart failure (HF).

Methods And Results: In eight sheep with pacing-induced HF, a 4-day infusion of Ucn-I (0.3 microg/kg/h) induced prompt (30 min) and sustained (4-day) increases in cardiac output (CO, Day 4: 1.

Endogenous urocortins reduce vascular tone and renin-aldosterone/endothelin activity in experimental heart failure.

Aims: To investigate the role of the endogenous urocortin peptides in heart failure (HF) through blockade of the corticotropin-releasing factor receptor 2 (CRF-R2).

Methods And Results: Eight sheep were administered the CRF-R2 antagonist CRF(9-41) (1.5 mg bolus) before (Normal) and after development of pacing-induced HF.

Combined inhibition of angiotensin II and endothelin suppresses the brain natriuretic peptide response to developing heart failure.

Blockade of AngII (angiotensin II) and ET (endothelin)-1, established and potential therapeutic strategies respectively, for heart failure, may have an adverse effect on the cardiac secretion of the natriuretic peptides, hormones with actions beneficial in this disease. The present study investigates the roles of AngII and ET-1 in regulating the stretch-induced release of the natriuretic peptides during the development of heart failure. On seven separate days, eight sheep underwent incremental left ventricular pacing (155, 190 and 225 beats/min for 90 min each) with concurrent infusions of a vehicle control, AngII, ET-1, AngII+ET-1, losartan [AT1 (AngII type 1) receptor antagonist], bosentan (ET(A)/ET(B) receptor antagonist) or losartan+bosentan.

Long-term adrenomedullin administration in experimental heart failure.

Short-term administration of adrenomedullin, a recently discovered peptide with potent vasodilator, natriuretic, and aldosterone-inhibitory actions, has beneficial effects in experimental and clinical heart failure. The effects of prolonged adrenomedullin administration have not previously been assessed in this setting. Consequently, in 16 sheep with pacing-induced heart failure, we infused either adrenomedullin (10 ng/kg per minute; n=8) or a vehicle control (Hemaccel; n=8) for 4 days.

Combined angiotensin-converting enzyme inhibition and adrenomedullin in an ovine model of heart failure.

Advances in the treatment of heart failure may require manipulation of neurohumoral responses to cardiac impairment in addition to the established strategy of angiotensin-converting enzyme (ACE) inhibition. Importantly, since new treatments are likely to be used in conjunction with ACE inhibition therapy, the effects of the combination of agents need to be assessed. Adrenomedullin (ADM) is a peptide with potent vasodilator and natriuretic actions.

Combined endopeptidase inhibition and adrenomedullin in sheep with experimental heart failure.

Adrenomedullin and the natriuretic peptides exert vasodilator, natriuretic, and aldosterone-inhibitory actions, making augmentation of both systems potential therapeutic strategies in heart failure. Adrenomedullin and an endopeptidase inhibitor (SCH32615) were administered separately and in combination in 8 sheep with heart failure. Compared with the control condition, SCH32615 (5 mg bolus+1 mg/kg per hour infusion for 3 hours) reduced arterial pressure, left atrial pressure, and peripheral resistance and increased cardiac output, urinary volume, sodium, creatinine, and cAMP excretion.