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Increasing product variety and expanding commercial offering create a challenge for companies in terms of keeping their product portfolio profitable and managing it through the entire lifecycle of products. Effective productization and product portfolio management (PPM) practices, supported by product structure considerations, may hold a key for product profitability over lifecycle. This article examines the current practices and improvement possibilities in productization and PPM, including the targets and key performance indicators (KPI), by considering the product lines of a global engineering company. The analysis utilizes the previous literature, company interviews, and relevant company materials. The article demonstrates company difficulties, which are stemming from inadequate definition of productization and imperfect PPM targets and KPIs over the product lifecycle. An initial framework is formed to support more holistic productization over product lifecycle alongside creating suitable PPM targets and KPIs.

The thrombospondin (TSP) family consists of five multimeric, multidomain calcium-binding glycoproteins that act as regulators of cell-cell and cell-matrix associations as well as interact with other extracellular matrix molecules affecting their function. Increasing interest on cardiac TSP-1, TSP-2 and TSP-4 has emerged, and they have been studied in cardiac hypertrophy, myocardial infarction, heart failure, atherosclerosis and aortic valve stenosis. The aim of this MiniReview is to summarize the current knowledge on each TSP in various cardiovascular pathologies. We specifically emphasize the role of TSPs in cardiac remodelling and evaluate TSPs as potential cardiovascular drug targets. Thrombospondin-1 (TSP-1) is the most studied TSP, being antiangiogenic and able to activate transforming growth factor-b. The functions of TSP-2 and TSP-4 are linked in maintaining the composition of the matrix of the hypertrophied heart, whereas there is very little knowledge on cardiac TSP-3 and TSP-5. TSP-1, TSP-2 and TSP-4 have been shown to affect cardiac remodelling in vivo, for example, by modulating matrix metalloproteinase and transforming growth factor-b activity, collagen synthesis, myofibroblast differentiation, cell death and stretch-mediated augmentation of cardiac contractility. The detrimental role for TSPs in cardiovascular pathophysiology has been clearly demonstrated in knockout mouse models, and augmentation of TSP signalling in the heart during stress and haemodynamic overload might be beneficial. In conclusion, the role of TSP-1, TSP-2 and TSP-4 in cardiac hypertrophy, remodelling after myocardial infarction, heart failure, atherosclerosis and aortic valve stenosis encourages further investigation to validate them as potential drug targets.

Background-B-type natriuretic peptide (BNP) is an endogenous peptide produced under physiological and pathological conditions mainly by ventricular myocytes. It has natriuretic, diuretic, blood pressure-lowering, and antifibrotic actions that could mediate cardiorenal protection in cardiovascular diseases. In the present study, we used BNP gene transfer to examine functional and structural effects of BNP on left ventricular (LV) remodeling. Methods and Results-Human BNP was overexpressed by using adenovirus-mediated gene delivery in normal rat hearts and in hearts during the remodeling process after infarction and in an experimental model of angiotensin II-mediated hypertension. In healthy hearts, BNP gene delivery into the anterior wall of the LV decreased myocardial fibrosis (PϽ0.01, nϭ7 to 8) and increased capillary density (PϽ0.05, nϭ7 to 8) associated with a 7.3-fold increase in LV BNP peptide levels. Overexpression of BNP improved LV fractional shortening by 22% (PϽ0.05, nϭ6 to 7) and ejection fraction by 19% (PϽ0.05, nϭ6 to 7) after infarction. The favorable effect of BNP gene delivery on cardiac function after infarction was associated with normalization of cardiac sarcoplasmic reticulum Ca 2ϩ -ATPase expression and phospholamban Thr17-phosphorylation. BNP gene delivery also improved fractional shortening and ejection fraction in angiotensin II-mediated hypertension as well as decreased myocardial fibrosis and LV collagen III mRNA levels but had no effect on angiogenesis or Ca 2ϩ -ATPase expression and phospholamban phosphorylation. Conclusions-Local intramyocardial BNP gene delivery improves cardiac function and attenuates adverse postinfarctionand angiotensin II-induced remodeling. These results also indicate that myocardial BNP has pleiotropic, contextdependent, favorable actions on cardiac function and suggest that BNP acts locally as a key mechanical load-activated regulator of angiogenesis and fibrosis. (Circ Heart Fail. 2011;4:483-495.)Key Words: B-type natriuretic peptide Ⅲ gene therapy Ⅲ heart failure Ⅲ myocardial infarction Ⅲ angiogenesis Ⅲ fibrosis H eart failure (HF) is one of the most common causes of cardiovascular morbidity and mortality, and its prevalence is rapidly increasing as the mean age of the population advances. 1 The major cause of systolic HF is coronary artery disease, whereas diastolic HF (HF with preserved ejection fraction [EF]) is more common in patients with hypertension. 2,3 Worsening of chronic systolic or diastolic dysfunction is the most common form of acute HF, accounting for a substantial number of hospitalizations with a poor prognosis. 4 A number of drugs, particularly ␤-blockers and drugs acting on the renin-angiotensin-aldosterone system, have been shown to improve survival in patients who have left ventricular (LV) systolic dysfunction. 2,3 However, identifying appropriate treatments for patients who have HF with preserved EF or acute HF has been a daunting task. [2][3][4] Clinical Perspective on p 495Atrial and B-type natriuretic peptides (ANP and BNP, re...