A Selection of Recent Papers as Recommended by the Advisory Panel

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The copyright in this work belongs to Radcliffe Medical Media. Only articles clearly marked with the CC BY-NC logo are published with the Creative Commons by Attribution Licence. The CC BY-NC option was not available for Radcliffe journals before 1 January 2019. Articles marked ‘Open Access’ but not marked ‘CC BY-NC’ are made freely accessible at the time of publication but are subject to standard copyright law regarding reproduction and distribution. Permission is required for reuse of this content.

A Cathepsin D-Cleaved 16kDa Form of Prolactin Mediates Postpartum Cardiomyopathy

Hilfiker-Kleiner D, Kaminski K, Podewski E, et al.

Cell, 2007;128(3):589–600

Postpartum cardiomyopathy (PPCM) is a disease of unknown aetiology exposing women to high risk of mortality after delivery. This study shows that female mice with a cardiomyocyte-specific deletion of STAT3 develop PPCM. In these mice, cardiac cathepsin D expression and activity is enhanced and associated with the generation of a cleaved antiangiogenic and proapoptotic 16 kDa form of the nursing hormone prolactin. Treatment with bro-mocriptine, an inhibitior of prolactin secretion, prevents the development of PPCM, whereas forced myocardial generation of 16 kDa prolactin impairs the cardiac capillary network and function, thereby recapitulating the cardiac phenotype of PPCM. Myocardial STAT3 protein levels are reduced and serum levels of activated CD and 16 kDa prolactin are elevated in PPCM patients. Thus, a biologically active derivative of the pregnancy hormone prolactin mediates PPCM, implying that inhibition of prolactin release may represent a novel therapeutic strategy for PPCM.

Detection of Coronary Microembolisation by Doppler Ultrasound in Patients with Stable Angina Pectoris Undergoing Elective Percutaneous Coronary Interventions

Bahrmann P, Werner GS, Heusch G, et al.

Circulation, 2007;115(5):600–8. Epub 2007 Jan 29

Intracoronary Doppler guidewires can be used for realtime detection and quantification of microembolism during percutaneous coronary interventions (PCIs). The study investigates whether the frequency of Doppler-detected microembolism is related to the incidence of myonecrosis during elective PCI. The study population included 52 consecutive patients with coronary artery disease who underwent elective PCI of a single-vessel stenosis. Using intracoronary Doppler ultrasound, the frequency of microembolism during PCI was compared in 22 patients with periprocedural non-ST-segment elevation myocardial infarctions (pNSTEMI) and 30 patients without pNSTEMI. The study concludes that patients with pNSTEMI had a significantly higher frequency of coronary microembolisation during PCI, and their systemic inflammatory response and microvascular impairment after PCI were more pronounced. Intracoronary Doppler ultrasound provides evidence that pNSTEMI in patients undergoing elective PCI is caused by microembolisation during the procedure.

Bidirectional Role of Tumor Necrosis Factor-alpha in Coronary Microembolisation: Progressive Contractile Dysfunction Versus Delayed Protection Against Infarction

Skyschally A, Gres P, Hoffmann S, et al.

Circ Res, 2007;100(1):140–46. Epub 2006 Dec 14

In patients with unstable angina, plaque rupture and coronary microembolization (ME) can precede complete coronary artery occlusion and impending infarction. ME-induced microinfarcts initiate an inflammatory reaction with increased tumor necrosis factor-alpha (TNF-alpha) expression, resulting in progressive contractile dysfunction. However, TNF-alpha is not only a negative inotrope, but can also protect the myocardium against infarction. In anaesthetised pigs, researchers studied whether ME protects against infarction when TNF-alpha expression is increased. ME was induced by intracoronary infusion of microspheres, while controls received saline. Groups 3 and 4 were pretreated with ovine TNF-alpha antibodies 30 minutes before ME or placebo, respectively. Ischaemia was induced six hours after ME when TNF-alpha was increased or after placebo. Infarct size was determined after two hours of reperfusion (triphenyl tetrazolium chloride staining). The study finds that in ME, TNF-alpha is responsible for both progressive contractile dysfunction and delayed protection against infarction.

Mechanisms Linking Obesity to Insulin Resistance and Type 2 Diabetes

Kahn SE, Hull RL, Utzschneider KM

Nature, 2006;444(7121):840–46

Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes. In obese individuals, adipose tissue releases increased amounts of non-esterified fatty acids, glycerol, hormones, pro-inflammatory cytokines and other factors that are involved in the development of insulin resistance. When insulin resistance is accompanied by dysfunction of pancreatic islet beta-cells – the cells that release insulin – failure to control blood glucose levels results. Abnormalities in beta-cell function are therefore critical in defining the risk and development of type 2 diabetes. This knowledge is fostering exploration of the molecular and genetic basis of the disease and new approaches to its treatment and prevention.

Mechanisms Linking Obesity with Cardiovascular Disease

Van Gaal LF, Mertens IL, De Block CE

Nature, 2006;444(7121):875–80

Obesity increases the risk of cardiovascular disease and premature death. Adipose tissue releases a large number of bioactive mediators that influence not only body weight homeostasis but also insulin resistance – the core feature of type 2 diabetes – as well as alterations in lipids, blood pressure, coagulation, fibrinolysis and inflammation, leading to endothelial dysfunction and atherosclerosis. There is growth in the understanding of the underlying mechanisms as well as the ways in which smoking and dyslipidaemia increase, and physical activity attenuates, the adverse effects of obesity on cardiovascular health.

Abdominal Obesity and Metabolic Syndrome

Despres JP, Lemieux I

Nature, 2006;444(7121):881–7

Metabolic syndrome is associated with abdominal obesity, blood lipid disorders, inflammation, insulin resistance or full-blown diabetes and increased risk of developing cardiovascular disease. Proposed criteria for identifying patients with metabolic syndrome have contributed greatly to preventative medicine, but the value of metabolic syndrome as a scientific concept remains controversial. The presence of metabolic syndrome alone cannot predict global cardiovascular disease risk. But abdominal obesity – the most prevalent manifestation of metabolic syndrome – is a marker of ‘dysfunctional adipose tissue’ and is of central importance in clinical diagnosis. Better risk-assessment algorithms are needed to quantify diabetes and cardiovascular disease risk on a global scale.