Beyond angiogenesis: the cardioprotective potential of fibroblast growth factor-2

In the field of cardiovascular research, a number of independent approaches have been explored to protect the heart from acute and chronic ischemic damage. Fibroblast growth factor-2 (FGF-2) recently has received considerable attention with respect to its angiogenic potential. While therapeutic angiogenesis may serve to salvage chronically ischemic myocardium, more acute treatments are in demand to increase cardiac resistance to injury (preconditioning) and to guard against secondary injury after an acute ischemic insult. Here, we look beyond the angiogenic potential of FGF-2 and examine its acute cardioprotective activity as demonstrated under experimental conditions, both as an agent of a preconditioning-like response and for secondary injury prevention at the time of reperfusion. Factors to consider in moving to the clinical setting will be discussed, including issues of dosage, treatment duration, and routes of administration. Finally, issues of safety and clinical trial design will be considered. The prospect of such a multipotent growth factor having clinical usefulness opens the door to effective treatment of both acute and chronic ischemic heart disease, something well worth the attention of the cardiovascular community.     

High Molecular Weight Fibroblast Growth Factor-2 in the Human Heart Is a Potential Target for Prevention of Cardiac Remodeling

Fibroblast growth factor 2 (FGF-2) is a multifunctional protein synthesized as high (Hi-) and low (Lo-) molecular weight isoforms. Studies using rodent models showed that Hi- and Lo-FGF-2 exert distinct biological activities: after myocardial infarction, rat Lo-FGF-2, but not Hi-FGF-2, promoted sustained cardioprotection and angiogenesis, while Hi-FGF-2, but not Lo-FGF-2, promoted myocardial hypertrophy and reduced contractile function. Because there is no information regarding Hi-FGF-2 in human myocardium, we undertook to investigate expression, regulation, secretion and potential tissue remodeling-associated activities of human cardiac (atrial) Hi-FGF-2. Human patient-derived atrial tissue extracts, as well as pericardial fluid, contained Hi-FGF-2 isoforms, comprising, respectively, 53%(±20 SD) and 68% (±25 SD) of total FGF-2, assessed by western blotting. Human atrial tissue-derived primary myofibroblasts (hMFs) expressed and secreted predominantly Hi-FGF-2, at about 80% of total. Angiotensin II (Ang II) up-regulated Hi-FGF-2 in hMFs, via activation of both type 1 and type 2 Ang II receptors; the ERK pathway; and matrix metalloprotease-2. Treatment of hMFs with neutralizing antibodies selective for human Hi-FGF-2 (neu-Ab^Hi-FGF-2) reduced accumulation of proteins associated with fibroblast-to-myofibroblast conversion and fibrosis, including α-smooth muscle actin, extra-domain A fibronectin, and procollagen. Stimulation of hMFs with recombinant human Hi-FGF-2 was significantly more potent than Lo-FGF-2 in upregulating inflammation-associated proteins such as pro-interleukin-1β and plasminogen-activator-inhibitor-1. Culture media conditioned by hMFs promoted cardiomyocyte hypertrophy, an effect that was prevented by neu-Ab^Hi-FGF-2 in vitro. In conclusion, we have documented that Hi-FGF-2 represents a substantial fraction of FGF-2 in human cardiac (atrial) tissue and in pericardial fluid, and have shown that human Hi-FGF-2, unlike Lo-FGF-2, promotes deleterious (pro-fibrotic, pro-inflammatory, and pro-hypertrophic) responses in vitro. Selective targeting of Hi-FGF-2 production may, therefore, reduce pathological remodelling in the human heart.     

Substrate and drainage system selection and slope stabilization in an intensive-type roof garden park: case study of Athens Concert Hall

The development of the green roof market in Greece and other Mediterranean countries in general has not been standardized, unlike in Germany and other northern European countries. The construction of successful sustainable green roofs relies mainly on the development and combination of integrated systems that include green roof stabilization and the appropriate selection of a substrate and drainage system to support sustainable plant growth. The current study provides a thorough review of the decision-making process associated with the selection of substrate, drainage, and slope-reinforcing materials for the Athens Concert Hall green roof park (2 ha). For the scope of this study, guidelines from different scientific fields were modified and combined to accommodate the specifics of this project and the Hellenic climatic conditions. The challenges addressed included a roof shell with 70 different inclinations, underground retaining walls and steps, and steep slopes that reached 70 % gradients. Selection of the appropriate materials and methodologies was supported by analyses that included granulometry, bulk density, hydraulic conductivity, moisture potential curves, organic matter content, and weight at saturation and field capacity. The drainage layer consisted of a bilayered system of pea gravel and sand combined with geotextiles. Substrate characteristics were defined by the analyses undertaken and adapted to the Hellenic climatic conditions. Geogrids and honeycomb geocells were utilized separately or in conjunction on inclined surfaces. Substrate moisture measurements performed at 150 locations on the green roof revealed increased moisture fluctuations (10–35 % v/v), which were mainly caused by the presence of the underground retaining walls.     

Adaptive and nonadaptive plasticity in changing environments: Implications for sexual species with different life history strategies

Populations adapt to novel environmental conditions by genetic changes or phenotypic plasticity. Plastic responses are generally faster and can buffer fitness losses under variable conditions. Plasticity is typically modeled as random noise and linear reaction norms that assume simple one‐to‐one genotype–phenotype maps and no limits to the phenotypic response. Most studies on plasticity have focused on its effect on population viability. However, it is not clear, whether the advantage of plasticity depends solely on environmental fluctuations or also on the genetic and demographic properties (life histories) of populations. Here we present an individual‐based model and study the relative importance of adaptive and nonadaptive plasticity for populations of sexual species with different life histories experiencing directional stochastic climate change. Environmental fluctuations were simulated using differentially autocorrelated climatic stochasticity or noise color, and scenarios of directional climate change. Nonadaptive plasticity was simulated as a random environmental effect on trait development, while adaptive plasticity as a linear, saturating, or sinusoidal reaction norm. The last two imposed limits to the plastic response and emphasized flexible interactions of the genotype with the environment. Interestingly, this assumption led to (a) smaller phenotypic than genotypic variance in the population (many‐to‐one genotype–phenotype map) and the coexistence of polymorphisms, and (b) the maintenance of higher genetic variation—compared to linear reaction norms and genetic determinism—even when the population was exposed to a constant environment for several generations. Limits to plasticity led to genetic accommodation, when costs were negligible, and to the appearance of cryptic variation when limits were exceeded. We found that adaptive plasticity promoted population persistence under red environmental noise and was particularly important for life histories with low fecundity. Populations producing more offspring could cope with environmental fluctuations solely by genetic changes or random plasticity, unless environmental change was too fast.     

Bioflavour production from orange peel hydrolysate using immobilized Saccharomyces cerevisiae

The rising trend of bioflavour synthesis by microorganisms is hindered by the high manufacturing costs, partially attributed to the cost of the starting material. To overcome this limitation, in the present study, dilute-acid hydrolysate of orange peel was employed as a low-cost, rich in fermentable sugars substrate for the production of flavour-active compounds by Saccharomyces cerevisiae. With this purpose, the use of immobilized cell technology to protect cells against the various inhibitory compounds present in the hydrolysate was evaluated with regard to yeast viability, carbon and nitrogen consumption and cell ability to produce flavour active compounds. For cell immobilization the encapsulation in Ca alginate beads was used. The results were compared with those obtained using free-cell system. Based on the data obtained immobilized cells showed better growth performance and increased ability for de novo synthesis of volatile esters of "fruity" aroma (phenylethyl acetate, ethyl hexanoate, octanoate, decanoate and dodecanoate) than those of free cells. The potential for in situ production of new formulations containing flavour-active compounds derive from yeast cells and also from essential oil of orange peel (limonene, α-terpineol) was demonstrated by the fact that bioflavour mixture was found to accumulate within the beads. Furthermore, the ability of the immobilized yeast to perform efficiently repeated batch fermentations of orange peel hydrolysate for bioflavour production was successfully maintained after six consecutive cycles of a total period of 240 h.