Hypertrophic Stimulation Increases β-actin Dynamics in Adult Feline Cardiomyocytes

The myocardium responds to hemodynamic stress through cellular growth and organ hypertrophy. The impact of cytoskeletal elements on this process, however, is not fully understood. While α-actin in cardiomyocytes governs muscle contraction in combination with the myosin motor, the exact role of β-actin has not been established. We hypothesized that in adult cardiomyocytes, as in non-myocytes, β-actin can facilitate cytoskeletal rearrangement within cytoskeletal structures such as Z-discs. Using a feline right ventricular pressure overload (RVPO) model, we measured the level and distribution of β-actin in normal and pressure overloaded myocardium. Resulting data demonstrated enriched levels of β-actin and enhanced translocation to the Triton-insoluble cytoskeletal and membrane skeletal complexes. In addition, RVPO in vivo and in vitro hypertrophic stimulation with endothelin (ET) or insulin in isolated adult cardiomyocytes enhanced the content of polymerized fraction (F-actin) of β-actin. To determine the localization and dynamics of β-actin, we adenovirally expressed GFP-tagged β-actin in isolated adult cardiomyocytes. The ectopically expressed β-actin-GFP localized to the Z-discs, costameres, and cell termini. Fluorescence recovery after photobleaching (FRAP) measurements of β-actin dynamics revealed that β-actin at the Z-discs is constantly being exchanged with β-actin from cytoplasmic pools and that this exchange is faster upon hypertrophic stimulation with ET or insulin. In addition, in electrically stimulated isolated adult cardiomyocytes, while β-actin overexpression improved cardiomyocyte contractility, immunoneutralization of β-actin resulted in a reduced contractility suggesting that β-actin could be important for the contractile function of adult cardiomyocytes. These studies demonstrate the presence and dynamics of β-actin in the adult cardiomyocyte and reinforce its usefulness in measuring cardiac cytoskeletal rearrangement during hypertrophic stimulation

Supplementary Materials_V3 FINAL.docx

Macrophages, Fibrosis, Heart Failure</p

Macrophage supplemental figures 1-4.pptx

Supplemental figures</p

Social Sustainability in EU-Based Urban Regeneration

The social dimension of sustainability has been underdefined and under researched when compared to the fields of economic and environmental sustainability. The paper explores the difficulty in understating the concept of social sustainability and the difficulty in operationalising the concept, items discussed in interviews. Through a qualitative content analysis, the paper highlights how the concept of social sustainability is positioned within the sustainability discourse and in a conflictual relationship with the economic and environmental sustainability. The concept of social sustainability is explored in the understanding of both a traditional and a new set of values, the latter being a weak instrument in operationalising compared to the former. The role of governance in navigating the interpretation of social sustainability is explored, with particular focus on policies as the result of decision-making process in governance. Partnerships structures are emphasised as an answer to incorporating social sustainability components of equity, empowerment, representation, and inclusion in policymaking. Urban regeneration is explored as an opportunity to change at local level, and EU policies are presented to highlight the discourse of urban regeneration to be more inclusive of social sustainability themes. Lastly, the case study of Leipzig East suggests the local authorities’ means to create a more socially sustainable governance structure during urban regeneration programmes. The case study shows strong local leadership and attention to power sharing during partnership schemes which involve public, private, and civic actors alike. The paper shows how Leipzig’s partnerships for urban regeneration fostered the creation of a more inclusive, democratic environment for both governance and residents alike

Supplementary Materials_V2-2.docx

supplemetal material and methods</p

Social Sustainability in EU-Based Urban Regeneration

The social dimension of sustainability has been underdefined and under researched when compared to the fields of economic and environmental sustainability. The paper explores the difficulty in understating the concept of social sustainability and the difficulty in operationalising the concept, items discussed in interviews. Through a qualitative content analysis, the paper highlights how the concept of social sustainability is positioned within the sustainability discourse and in a conflictual relationship with the economic and environmental sustainability. The concept of social sustainability is explored in the understanding of both a traditional and a new set of values, the latter being a weak instrument in operationalising compared to the former. The role of governance in navigating the interpretation of social sustainability is explored, with particular focus on policies as the result of decision-making process in governance. Partnerships structures are emphasised as an answer to incorporating social sustainability components of equity, empowerment, representation, and inclusion in policymaking. Urban regeneration is explored as an opportunity to change at local level, and EU policies are presented to highlight the discourse of urban regeneration to be more inclusive of social sustainability themes. Lastly, the case study of Leipzig East suggests the local authorities’ means to create a more socially sustainable governance structure during urban regeneration programmes. The case study shows strong local leadership and attention to power sharing during partnership schemes which involve public, private, and civic actors alike. The paper shows how Leipzig’s partnerships for urban regeneration fostered the creation of a more inclusive, democratic environment for both governance and residents alike

Cardiac extracellular matrix remodeling: Fibrillar collagens and Secreted Protein Acidic and Rich in Cysteine (SPARC)

The cardiac interstitium is a unique and adaptable extracellular matrix (ECM) that provides a milieu in which myocytes, fibroblasts, and endothelial cells communicate and function. The composition of the ECM in the heart includes structural proteins such as fibrillar collagens and matricellular proteins that modulate cell:ECM interaction. Secreted Protein Acidic and Rich in Cysteine (SPARC), a collagen-binding matricellular protein, serves a key role in collagen assembly into the ECM. Recent results demonstrated increased cardiac rupture, dysfunction and mortality in SPARC-null mice in response to myocardial infarction that was associated with a decreased capacity to generate organized, mature collagen fibers. In response to pressure overload induced-hypertrophy, the decrease in insoluble collagen incorporation in the left ventricle of SPARC-null hearts was coincident with diminished ventricular stiffness in comparison to WT mice with pressure overload. This review will focus on the role of SPARC in the regulation of interstitial collagen during cardiac remodeling following myocardial infarction and pressure overload with a discussion of potential cellular mechanisms that control SPARC-dependent collagen assembly in the heart