Vasculogenesis and angiogenesis: Extracellular matrix remodeling in coronary collateral arteries and the ischemic heart

Heart failure secondary to ischemic cardiomyopathy is the primary cause of cardiovascular mortality. The promise of the collateral circulation lies in its potential to alter the course of the natural history of coronary heart disease. The collateral circulation of the heart is responsible for supplying blood and oxygen to the myocardium at ischemic risk following severe stenosis and reduced vasoelasticity function of a major coronary artery. In response to flow, stress, and pressure, collateral vessels are restructured and remodeled. Vascular remodeling by its very nature implies synthesis and degradation of extracellular matrix components in the vessel wall. Under normal physiological conditions proteinases that break down the specialized matrix are tightly regulated by antiproteinases. The balance between proteinase and antiproteinase influences is discoordinated during collateral development which leads to adaptive changes in the structure, function, and regulation of extracellular matrix components in the vessel wall. The role of extracellular matrix components in coronary collateral vessel formation in a canine model of chronic coronary artery occlusion has been demonstrated. The role of matrix proteinases and antiproteinases in the collateral vessel play a significant role in the underlying mechanisms of collateral development. This review presents new and significant information regarding the role of extracellular matrix proteinases and antiproteinases in vascular remodeling, function, and collateral development. Such information will have a significant impact on the understanding of the basic biology of the vascular extracellular matrix turnover, remodeling, and function as well as on elucidating potential avenues for pharmacological approaches designed to increase collateral formation and optimize myocardial blood flow in the treatment of ischemic heart disease. J. Cell. Biochem. 65:388–394. © 1997 Wiley-Liss, Inc.     

Medial and Lateral Entorhinal Cortex Differentially Excite Deep versus Superficial CA1 Pyramidal Neurons

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Effects of single low-temperature sauna bathing in patients with severe motor and intellectual disabilities

We have previously reported that thermal vasodilation following warm-water bathing and low-temperature sauna bathing (LTSB) at 60 degrees C for 15 min improves the cardiac function in patients with congestive heart failure. Through a comparative before-and-after study, we studied the hemodynamic and clinical effects of single exposure to LTSB in cerebral palsy (CP) patients who usually suffer from chilled extremities and low cardiac output. The study population comprised 16 patients ranging between 19 and 53 years with severe motor and intellectual disabilities. Noninvasive methods were used to estimate the systemic and peripheral circulatory changes before and after LTSB. Using blood flow velocity analysis, the pulsatile and resistive indexes of the peripheral arteries of the patients' lower limbs were calculated. Following LTSB, the patients' deep body temperature increased significantly by 1 degrees C. Their heart rates increased and blood pressure decreased slightly. The total peripheral resistance decreased by 11%, and the cardiac output increased by 14%. There was significant improvement in the parameters that are indicative of the peripheral circulatory status, including the skin blood flow, blood flow velocity, pulsatile index, and resistive index. Numbness and chronic myalgia of the extremities decreased. There were no adverse side effects. Thus, it can be concluded that LTSB improves the peripheral circulation in CP patients.     

扶正活血祛瘀法治疗慢性足底溃疡的临床疗效观察

目的观察扶正活血祛瘀法治疗慢性足底溃疡的临床疗效。方法采用四妙勇安汤加减内服,红萝卜加马齿苋煎液浸泡外洗溃疡处,外敷呋喃西林纱布保护伤口的综合治疗方法。结果36例中治愈27例,占75．0％;好转6例,占16．7％;无效3例,占8．3％．姑论以扶正活血祛痰法内服为主,结合红萝卜加马齿苋煎液浸泡外洗与呋喃西林纱布外敷治疗慢性足底溃疡有较好的临床疗效．     

Circulatory system in chicken skeletal muscle in the second half of embryogenesis: Shape,blood flow,and vascular reactivity

A restructuring of the capillary bed—from the embryonic structure with a three-dimensional network of wide and long protocapillaries to the mature structure with high density of thin and short capillaries along the fibers—has been demonstrated in the chick skeletal muscle on embryonic days 10–19 by morphometric analysis. In this case, the specific blood flow and capillary luminal area per cm³ of the muscle remained unaltered, while the blood volume in it significantly dropped. The response of muscle circulation to nitroprusside (increase) and noradrenaline (decrease) appeared in 19-day-old embryos, but this response could develop only under conditions of initially low or high blood flow, respectively. We propose that the arterial trunk lumen area to the total capillary lumen area remains constant as the intraorganic circulation is formed, which provides for the required linear blood velocity in capillaries.     

Live optical projection tomography

Optical projection tomography (OPT) is a technology ideally suited for imaging embryonic organs. We emphasize here recent successes in translating this potential into the field of live imaging. Live OPT (also known as 4D OPT, or time-lapse OPT) is already in position to accumulate good quantitative data on the developmental dynamics of organogenesis, a prerequisite for building realistic computer models and tackling new biological problems. Yet, live OPT is being further developed by merging state-of-the-art mouse embryo culture with the OPT system. We discuss the technological challenges that this entails and the prospects for expansion of this molecular imaging technique into a wider range of applications.     

Bile acids and their nuclear receptor FXR: Relevance for hepatobiliary and gastrointestinal disease

The nuclear receptor Farnesoid X Receptor (FXR) critically regulates nascent bile formation and bile acid enterohepatic circulation. Bile acids and FXR play a pivotal role in regulating hepatic inflammation and regeneration as well as in regulating extent of inflammatory responses, barrier function and prevention of bacterial translocation in the intestinal tract. Recent evidence suggests, that the bile acid–FXR interaction is involved in the pathophysiology of a wide range of diseases of the liver, biliary and gastrointestinal tract, such as cholestatic and inflammatory liver diseases and hepatocellular carcinoma, inflammatory bowel disease and inflammation-associated cancer of the colon and esophagus. In this review we discuss current knowledge of the role the bile acid–FXR interaction has in (patho)physiology of the liver, biliary and gastrointestinal tract, and proposed underlying mechanisms, based on in vitro data and experimental animal models. Given the availability of highly potent synthetic FXR agonists, we focus particularly on potential relevance for human disease.     

THIS ARTICLE HAS BEEN RETRACTED: What caused the mid‐Holocene forest decline on the eastern Tibet‐Qinghai Plateau?

Aim Atmospheric CO₂ concentrations depend, in part, on the amount of biomass locked up in terrestrial vegetation. Information on the causes of a broad‐scale vegetation transition and associated loss of biomass is thus of critical interest for understanding global palaeoclimatic changes. Pollen records from the north‐eastern Tibet‐Qinghai Plateau reveal a dramatic and extensive forest decline beginning c. 6000 cal. yr bp . The aim of this study is to elucidate the causes of this regional‐scale change from high‐biomass forest to low‐biomass steppe on the Tibet‐Qinghai Plateau during the second half of the Holocene. Location Our study focuses on the north‐eastern Tibet‐Qinghai Plateau. Stratigraphical data used are from Qinghai Lake (3200 m a.s.l., 36°32′–37°15′ N, 99°36′–100°47′ E). Methods We apply a modern pollen‐precipitation transfer function from the eastern and north‐eastern Tibet‐Qinghai Plateau to fossil pollen spectra from Qinghai Lake to reconstruct annual precipitation changes during the Holocene. The reconstructions are compared to a stable oxygen‐isotope record from the same sediment core and to results from two transient climate model simulations. Results The pollen‐based precipitation reconstruction covering the Holocene parallels moisture changes inferred from the stable oxygen‐isotope record. Furthermore, these results are in close agreement with simulated model‐based past annual precipitation changes. Main conclusions In the light of these data and the model results, we conclude that it is not necessary to attribute the broad‐scale forest decline to human activity. Climate change as a result of changes in the intensity of the East Asian Summer Monsoon in the mid‐Holocene is the most parsimonious explanation for the widespread forest decline on the Tibet‐Qinghai Plateau. Moreover, climate feedback from a reduced forest cover accentuates increasingly drier conditions in the area, indicating complex vegetation–climate interactions during this major ecological change.     

Adenosine receptor-mediated coronary vascular protection in post-ischemic mouse heart

This study evaluated the ability of A1 and A3 adenosine receptor (AR) agonism, and A1, A2A, A2B and A3AR antagonism (revealing "intrinsic" responses), to modify post-ischemic coronary dysfunction in mouse heart. Vascular function was assessed before and after 20 min global ischemia and 30-45 min reperfusion in Langendorff perfused C57/Bl6 mouse hearts. Ischemic insult impaired coronary sensitivity to the endothelial-dependent dilators ADP (pEC50=6.8+/-0.1 vs. 7.6+/-0.1, non-ischemic) and acetylcholine (pEC50=6.1+/-0.1 vs. 7.3+/-0.1 in non-ischemic), and for the mixed endothelial-dependent/independent dilator 2-chloroadenosine (pEC50=7.5+/-0.1 vs. 8.4+/-0.1, non-ischemic). Endothelium-independent dilation in response to nitroprusside was unaltered (pEC50=7.0+/-0.1 vs. 7.1+/-0.1 in non-ischemic). Pre-treatment with a selective A1AR agonist (50 nM CHA) failed to modify coronary dysfunction, whereas A1AR antagonism (200 nM DPCPX) worsened the effects of I/R (2-chloroadenosine pEC50=6.9+/-0.1). Conversely, A3AR agonism (100 nM Cl-IB-MECA) did reduce effects of I/R (pEC50s=8.0+/-0.1 and 7.3+/-0.1 for 2-chloroadenosine and ADP, respectively), whereas antagonism (100 nM MRS1220) was without effect. While A2AAR agonism could not be assessed (due to pronounced vasodilatation), A2AAR antagonism (100 nM SCH58261) was found to exert no effect, and antagonism of A2BARs (50 nM MRS1754) was also ineffective. The protective actions of A3AR agonism were also manifest as improved reactive hyperemic responses. Interestingly, post-ischemic coronary dysfunction was also limited by: Na+-H+ exchange (NHE) inhibition with 10 or 50 microM BIIB-513 (2-chloroadenosine pEC50s=7.8+/-0.1, either dose), an effect not additive with A3AR agonism; Ca2+ antagonism with 0.3 microM verapamil (2-chloroadenosine pEC50=7.9+/-0.1); and Ca2+ desensitization with 5 mM BDM (2-chloroadenosine pEC50=7.8+/-0.1). In contrast, endothelin antagonism (200 nM PD142893) and anti-oxidant therapy (300 microM MPG+150 U/ml SOD+600 U/ml catalase) were ineffective. Our data collectively confirm that ischemia selectively impairs endothelial function and reactive hyperemia independently of blood cells. Vascular injury is intrinsically limited by endogenous (but not exogenous) activation of A1ARs, whereas exogenous A3AR activation further limits dysfunction (improving post-ischemic vasoregulation). Finally, findings suggest this form of post-ischemic coronary injury is unrelated to endothelin or oxidant stress, but may involve modulation of Ca2+ overload and/or related ionic perturbations.