Pub Date : 2010-01-01DOI: 10.2174/1874120701007010001
Arun K Singhal, J David Symons, Sihem Boudina, Bharat Jaishy, Yan-Ting Shiu
Minimizing myocardial ischemia-reperfusion injury has broad clinical implications and is a critical mediator of cardiac surgical outcomes. "Ischemic injury" results from a restriction in blood supply leading to a mismatch between oxygen supply and demand of a sufficient intensity and/or duration that leads to cell necrosis, whereas ischemia-reperfusion injury occurs when blood supply is restored after a period of ischemia and is usually associated with apoptosis (i.e. programmed cell death). Compared to vascular endothelial cells, cardiac myocytes are more sensitive to ischemic injury and have received the most attention in preventing myocardial ischemia-reperfusion injury. Many comprehensive reviews exist on various aspects of myocardial ischemia-reperfusion injury. The purpose of this review is to examine the role of vascular endothelial cells in myocardial ischemia-reperfusion injury, and to stimulate further research in this exciting and clinically relevant area. Two specific areas that are addressed include: 1) data suggesting that coronary endothelial cells are critical mediators of myocardial dysfunction after ischemia-reperfusion injury; and 2) the involvement of the mitochondrial permeability transition pore in endothelial cell death as a result of an ischemia-reperfusion insult. Elucidating the cellular signaling pathway(s) that leads to endothelial cell injury and/or death in response to ischemia-reperfusion is a key component to developing clinically applicable strategies that might minimize myocardial ischemia-reperfusion injury.
{"title":"Role of Endothelial Cells in Myocardial Ischemia-Reperfusion Injury.","authors":"Arun K Singhal, J David Symons, Sihem Boudina, Bharat Jaishy, Yan-Ting Shiu","doi":"10.2174/1874120701007010001","DOIUrl":"https://doi.org/10.2174/1874120701007010001","url":null,"abstract":"<p><p>Minimizing myocardial ischemia-reperfusion injury has broad clinical implications and is a critical mediator of cardiac surgical outcomes. \"Ischemic injury\" results from a restriction in blood supply leading to a mismatch between oxygen supply and demand of a sufficient intensity and/or duration that leads to cell necrosis, whereas ischemia-reperfusion injury occurs when blood supply is restored after a period of ischemia and is usually associated with apoptosis (i.e. programmed cell death). Compared to vascular endothelial cells, cardiac myocytes are more sensitive to ischemic injury and have received the most attention in preventing myocardial ischemia-reperfusion injury. Many comprehensive reviews exist on various aspects of myocardial ischemia-reperfusion injury. The purpose of this review is to examine the role of vascular endothelial cells in myocardial ischemia-reperfusion injury, and to stimulate further research in this exciting and clinically relevant area. Two specific areas that are addressed include: 1) data suggesting that coronary endothelial cells are critical mediators of myocardial dysfunction after ischemia-reperfusion injury; and 2) the involvement of the mitochondrial permeability transition pore in endothelial cell death as a result of an ischemia-reperfusion insult. Elucidating the cellular signaling pathway(s) that leads to endothelial cell injury and/or death in response to ischemia-reperfusion is a key component to developing clinically applicable strategies that might minimize myocardial ischemia-reperfusion injury.</p>","PeriodicalId":88793,"journal":{"name":"Vascular disease prevention","volume":"7 ","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4280830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32949273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-06-24DOI: 10.2174/1567270000906010170
M. Fujihara, S. Wakamoto, H. Azuma, H. Ikeda
Vascular endothelial cells regulate the passage of fluids, solutes, and cells from the vascular space to the tis- sues. Disruption of vascular integrity is involved in the pathogenesis of inflammatory diseases including transfusion- related acute lung injury (TRALI), a most severe nonhemolytic transfusion reaction with symptoms such as dyspnea and/or hypotension and fever. Pulmonary edema, due to increased vascular permeability for macromolecules and plasma, is a hallmark of TRALI. The mortality rate of TRALI ranges from 5 to 10%. While donor antibodies (Abs) against human leukocyte antigen (HLA) class I and granulocytes are regarded as causative factors, various clinical studies have demon- strated the roles of anti-HLA class II-Ab on the etiology of TRALI, although the detailed mechanisms have not been clari- fied. Over several years we have investigated to clarify the underlying mechanism by which anti-HLA class II Abs cause an increase in endothelial permeability. In this review, we show that anti-HLA class II Ab generates proinflammatory cy- tokines and chemokines from HLA class II positive mononuclear cells of peripheral blood in an Fc R-dependent manner. As a result, the produced interleukin-1 and tumor necrosis factor- lead to increased endothelial permeability via the nu- clear factor- B pathway but not apoptosis of endothelial cells. These findings provide a better understanding of the roles of anti-HLA class II Ab in the etiology of TRALI.
{"title":"Involvement of Human Leukocyte Antigen Class II Antibody in Pathogenesis of Transfusion-Related Acute Lung Injury (TRALI): Vascular Permeability Enhancement","authors":"M. Fujihara, S. Wakamoto, H. Azuma, H. Ikeda","doi":"10.2174/1567270000906010170","DOIUrl":"https://doi.org/10.2174/1567270000906010170","url":null,"abstract":"Vascular endothelial cells regulate the passage of fluids, solutes, and cells from the vascular space to the tis- sues. Disruption of vascular integrity is involved in the pathogenesis of inflammatory diseases including transfusion- related acute lung injury (TRALI), a most severe nonhemolytic transfusion reaction with symptoms such as dyspnea and/or hypotension and fever. Pulmonary edema, due to increased vascular permeability for macromolecules and plasma, is a hallmark of TRALI. The mortality rate of TRALI ranges from 5 to 10%. While donor antibodies (Abs) against human leukocyte antigen (HLA) class I and granulocytes are regarded as causative factors, various clinical studies have demon- strated the roles of anti-HLA class II-Ab on the etiology of TRALI, although the detailed mechanisms have not been clari- fied. Over several years we have investigated to clarify the underlying mechanism by which anti-HLA class II Abs cause an increase in endothelial permeability. In this review, we show that anti-HLA class II Ab generates proinflammatory cy- tokines and chemokines from HLA class II positive mononuclear cells of peripheral blood in an Fc R-dependent manner. As a result, the produced interleukin-1 and tumor necrosis factor- lead to increased endothelial permeability via the nu- clear factor- B pathway but not apoptosis of endothelial cells. These findings provide a better understanding of the roles of anti-HLA class II Ab in the etiology of TRALI.","PeriodicalId":88793,"journal":{"name":"Vascular disease prevention","volume":"6 1","pages":"170-177"},"PeriodicalIF":0.0,"publicationDate":"2009-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67889063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-06-16DOI: 10.2174/1567270000906010163
K. Matsubara, Y. Matsubara, Masaharu Ito
Preeclampsia is a major cause of maternal and perinatal mortality. Although preeclampsia may be caused by several factors, endothelial cell dysfunction has been proposed as the main pathophysiological cause. Dysfunctional endo- thelium in the uteroplacental circulation not only increases peripheral vascular resistance, but also affects generalized vasoconstriction via humoral factors released from the placenta. A standard method for predicting and preventing preeclampsia has yet to be developed; however, the analysis of a combination of biochemical markers, particularly mark- ers related to vascular dysfunction, may enhance our ability to predict and prevent preeclampsia in the near future.
{"title":"The Utility of Vascular Dysfunction Studies in the Prediction and Prevention of Preeclampsia: A Historical Review","authors":"K. Matsubara, Y. Matsubara, Masaharu Ito","doi":"10.2174/1567270000906010163","DOIUrl":"https://doi.org/10.2174/1567270000906010163","url":null,"abstract":"Preeclampsia is a major cause of maternal and perinatal mortality. Although preeclampsia may be caused by several factors, endothelial cell dysfunction has been proposed as the main pathophysiological cause. Dysfunctional endo- thelium in the uteroplacental circulation not only increases peripheral vascular resistance, but also affects generalized vasoconstriction via humoral factors released from the placenta. A standard method for predicting and preventing preeclampsia has yet to be developed; however, the analysis of a combination of biochemical markers, particularly mark- ers related to vascular dysfunction, may enhance our ability to predict and prevent preeclampsia in the near future.","PeriodicalId":88793,"journal":{"name":"Vascular disease prevention","volume":"6 1","pages":"163-169"},"PeriodicalIF":0.0,"publicationDate":"2009-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67889017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-05-05DOI: 10.2174/1567270000906010157
G. Seki, Hideomi Yamada, Yuehong Li, S. Horita, N. Ishizaka, K. Koike, T. Fujita
Chronic kidney disease (CKD) is now widely recognized as a significant risk factor for cardiovascular disease (CVD). Chronic angiotensin II (Ang II) stimulation facilitates tissue hyperplasia, hypertrophy, and inflammation, and the current medical strategy for CKD is primarily based on the suppression of rein-angiotensin system. Since Ang II induces hypertension through both vasoconstriction and sodium retention, the understanding of vascular and renal actions of Ang II is essential for the better management of CKD and CVD. Ang II is coupled to a variety of intracellular signaling path- ways depending on cell types, and Ang II type 1 receptor (AT1) is thought to be responsible for most, if not all, of the car- diovascular effects of Ang II. Recent studies have suggested that the MEK/ERK pathway plays an important role in Ang II-mediated vascular smooth muscle contraction, where cytosolic phospholipase A2 (cPLA2)/P450 pathway has a positive feedback effect. Interestingly, the MEK/ERK pathway has been also shown to mediate the stimulatory effect of Ang II on renal proximal transport. However, the cPLA2/P450 pathway has a negative feedback effect on the Ang II-mediated ERK activation in renal proximal tubules. Thus, arachidonic acid metabolites seem to play quite contrasting roles in the Ang II- mediated ERK activation in vascular and renal tissues. This article will be focused on the roles of MEK/ERK pathway in vascular and renal tubular actions of Ang II.
{"title":"Roles of MEK/ERK Pathway in Vascular and Renal Tubular Actions of Angiotensin II","authors":"G. Seki, Hideomi Yamada, Yuehong Li, S. Horita, N. Ishizaka, K. Koike, T. Fujita","doi":"10.2174/1567270000906010157","DOIUrl":"https://doi.org/10.2174/1567270000906010157","url":null,"abstract":"Chronic kidney disease (CKD) is now widely recognized as a significant risk factor for cardiovascular disease (CVD). Chronic angiotensin II (Ang II) stimulation facilitates tissue hyperplasia, hypertrophy, and inflammation, and the current medical strategy for CKD is primarily based on the suppression of rein-angiotensin system. Since Ang II induces hypertension through both vasoconstriction and sodium retention, the understanding of vascular and renal actions of Ang II is essential for the better management of CKD and CVD. Ang II is coupled to a variety of intracellular signaling path- ways depending on cell types, and Ang II type 1 receptor (AT1) is thought to be responsible for most, if not all, of the car- diovascular effects of Ang II. Recent studies have suggested that the MEK/ERK pathway plays an important role in Ang II-mediated vascular smooth muscle contraction, where cytosolic phospholipase A2 (cPLA2)/P450 pathway has a positive feedback effect. Interestingly, the MEK/ERK pathway has been also shown to mediate the stimulatory effect of Ang II on renal proximal transport. However, the cPLA2/P450 pathway has a negative feedback effect on the Ang II-mediated ERK activation in renal proximal tubules. Thus, arachidonic acid metabolites seem to play quite contrasting roles in the Ang II- mediated ERK activation in vascular and renal tissues. This article will be focused on the roles of MEK/ERK pathway in vascular and renal tubular actions of Ang II.","PeriodicalId":88793,"journal":{"name":"Vascular disease prevention","volume":"6 1","pages":"157-162"},"PeriodicalIF":0.0,"publicationDate":"2009-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67888927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-04-24DOI: 10.2174/1567270000906010142
H. Satoh, Saori Matsui, H. Hayashi
Serum aldosterone levels are often elevated in patients with heart failure and are associated with poor clinical outcomes. Aldosterone can be produced in extra-adrenal tissues including the heart, and the local increase in aldosterone exerts deleterious effects on heart structure and function. Aldosterone has 2 types of effects on intracellular ion milieu and cellular function. One is the classical genomic effect in which aldosterone combines with the intracellular mineralocorti- coid receptor, transfers to the nucleus, and stimulates synthesis of various proteins. Another is the non-genomic effect that expresses within minutes without synthesizing proteins. The non-genomic effects of aldosterone are less proved in the heart, but it has been shown that aldosterone rapidly activates Na + influxes via Na + -K + -2Cl - co-transport and Na + /H + ex- change, resulting in an increase in intracellular Na + concentration and intracellular alkalinization. These changes in intra- cellular ion milieu cause positive inotropy, cell swelling, and generation of reactive oxygen species. Thus, the non- genomic effects of aldosterone may contribute, in concert with the genomic effects, to cardiac hypertrophy, fibrosis, and remodeling. This review will discuss the experimental studies examining the mechanisms and physiological/patho- physiological relevance regarding the non-genomic effects of aldosterone in the heart.
{"title":"Non-Genomic Effects of Aldosterone on Intracellular Ion Regulation and Cell Function in the Heart","authors":"H. Satoh, Saori Matsui, H. Hayashi","doi":"10.2174/1567270000906010142","DOIUrl":"https://doi.org/10.2174/1567270000906010142","url":null,"abstract":"Serum aldosterone levels are often elevated in patients with heart failure and are associated with poor clinical outcomes. Aldosterone can be produced in extra-adrenal tissues including the heart, and the local increase in aldosterone exerts deleterious effects on heart structure and function. Aldosterone has 2 types of effects on intracellular ion milieu and cellular function. One is the classical genomic effect in which aldosterone combines with the intracellular mineralocorti- coid receptor, transfers to the nucleus, and stimulates synthesis of various proteins. Another is the non-genomic effect that expresses within minutes without synthesizing proteins. The non-genomic effects of aldosterone are less proved in the heart, but it has been shown that aldosterone rapidly activates Na + influxes via Na + -K + -2Cl - co-transport and Na + /H + ex- change, resulting in an increase in intracellular Na + concentration and intracellular alkalinization. These changes in intra- cellular ion milieu cause positive inotropy, cell swelling, and generation of reactive oxygen species. Thus, the non- genomic effects of aldosterone may contribute, in concert with the genomic effects, to cardiac hypertrophy, fibrosis, and remodeling. This review will discuss the experimental studies examining the mechanisms and physiological/patho- physiological relevance regarding the non-genomic effects of aldosterone in the heart.","PeriodicalId":88793,"journal":{"name":"Vascular disease prevention","volume":"6 1","pages":"142-147"},"PeriodicalIF":0.0,"publicationDate":"2009-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67888899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-04-24DOI: 10.2174/1567270000906010139
M. Bedi, Shilpa Khullar, V. P. Varshney
There is much evidence regarding autonomic dysfunction in obesity in adults, but information on autonomic status in obese children is scant. In the present study autonomic function tests were conducted in 30 normal and 30 obese children aged between 5 and 10 years. We performed tests for parasympathetic function (resting heart rate, S:L ratio (standing to lying ratio), 30:15 ratio and Valsalva ratio) and tests to assess sympathetic function (blood pressure response to hand grip test and cold pressor response). The children were classified as normal and obese on the basis of BMI (body mass index). Children with BMI between 20 to 24.9 were classified as normal and those with BMI > 30 as obese. The mean values of hand grip test and cold pressor response were significantly lower in the study group compared with controls (P < 0.05), however the Valsalva ratio was higher in the obese compared with normal children. Hence, our study showed compromised autonomic nervous system functions in the obese group compared with controls
{"title":"Assessment of Autonomic Function Activity in Obese Children","authors":"M. Bedi, Shilpa Khullar, V. P. Varshney","doi":"10.2174/1567270000906010139","DOIUrl":"https://doi.org/10.2174/1567270000906010139","url":null,"abstract":"There is much evidence regarding autonomic dysfunction in obesity in adults, but information on autonomic status in obese children is scant. In the present study autonomic function tests were conducted in 30 normal and 30 obese children aged between 5 and 10 years. We performed tests for parasympathetic function (resting heart rate, S:L ratio (standing to lying ratio), 30:15 ratio and Valsalva ratio) and tests to assess sympathetic function (blood pressure response to hand grip test and cold pressor response). The children were classified as normal and obese on the basis of BMI (body mass index). Children with BMI between 20 to 24.9 were classified as normal and those with BMI > 30 as obese. The mean values of hand grip test and cold pressor response were significantly lower in the study group compared with controls (P < 0.05), however the Valsalva ratio was higher in the obese compared with normal children. Hence, our study showed compromised autonomic nervous system functions in the obese group compared with controls","PeriodicalId":88793,"journal":{"name":"Vascular disease prevention","volume":"6 1","pages":"139-141"},"PeriodicalIF":0.0,"publicationDate":"2009-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67888888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-04-24DOI: 10.2174/1567270000906010148
A. Arce-Esquivel, B. Manor, Li Li, M. Welsch
Background: Peripheral neuropathy is characterized by a reduction/alteration in sensation, muscle weakness and chronic fatigue, which may compromise physical function. Mechanisms contributing to the development of PN may include poor vascular function. The purpose was to examine the relationship between measures of vascular and physical function in individuals with peripheral neuropathy. Methods: This study used a cross sectional design to examine 59 indi- viduals with peripheral neuropathy. Strain gauge plethysmography was used to assess lower leg vascular function. Spe- cific measures included resting in-flow, venous outflow (VOt1/2), and reactive hyperemic blood flow (RHBF). Physical function was examined using a 6-minute walk (6MWD), the timed up and go (TUG) test, and isokinetic knee extension (KE) and flexion (KF). Results: RHBF was related to the TUG (r=-0.31, p=0.02) and 6MWD (r=0.37, p=0.007). Patients in the top tertile of the TUG had significantly higher peak RHBF compared to the lower tertiles. Those who walked 400m. Finally, those in the top tertile of KF ex- hibited faster VOt1/2. Conclusions: These data indicate a relationship between vascular and physical function in peripheral neuropathy. Individuals with greater physical function exhibit more favorable measures of arterial inflow and venous out- flow.
{"title":"Relationship Between Vascular and Physical Function in Individuals with Peripheral Neuropathy","authors":"A. Arce-Esquivel, B. Manor, Li Li, M. Welsch","doi":"10.2174/1567270000906010148","DOIUrl":"https://doi.org/10.2174/1567270000906010148","url":null,"abstract":"Background: Peripheral neuropathy is characterized by a reduction/alteration in sensation, muscle weakness and chronic fatigue, which may compromise physical function. Mechanisms contributing to the development of PN may include poor vascular function. The purpose was to examine the relationship between measures of vascular and physical function in individuals with peripheral neuropathy. Methods: This study used a cross sectional design to examine 59 indi- viduals with peripheral neuropathy. Strain gauge plethysmography was used to assess lower leg vascular function. Spe- cific measures included resting in-flow, venous outflow (VOt1/2), and reactive hyperemic blood flow (RHBF). Physical function was examined using a 6-minute walk (6MWD), the timed up and go (TUG) test, and isokinetic knee extension (KE) and flexion (KF). Results: RHBF was related to the TUG (r=-0.31, p=0.02) and 6MWD (r=0.37, p=0.007). Patients in the top tertile of the TUG had significantly higher peak RHBF compared to the lower tertiles. Those who walked 400m. Finally, those in the top tertile of KF ex- hibited faster VOt1/2. Conclusions: These data indicate a relationship between vascular and physical function in peripheral neuropathy. Individuals with greater physical function exhibit more favorable measures of arterial inflow and venous out- flow.","PeriodicalId":88793,"journal":{"name":"Vascular disease prevention","volume":"6 1","pages":"148-156"},"PeriodicalIF":0.0,"publicationDate":"2009-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67888912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-04-24DOI: 10.2174/1567270000906010131
Ashima Bhattacharjee, Justine R. Smith
Endothelial cells form the lining of the vasculature. Despite the continuity of this layer throughout the body, endothelial cells exhibit remarkable heterogeneity in structure, molecular composition and activity: between sites; and in response to different exposures. One important consequence of endothelial diversity is the localized nature of many vascu- lar disorders. To date a limited number of studies have attempted to define unique phenotypic features of the different in- traocular endothelial subpopulations, which include the endothelial cells of vascular beds in the iris, the choroid and the retina. Differences that distinguish endothelial cells in the circulations of the choroid and the retina, in particular, are be- lieved to be major etiological factors controlling the specific involvement of the two tissues in some of the most common blinding diseases. Age-related macular degeneration involves choroid, and diabetic retinopathy and posterior uveitis are primarily diseases of the retina. Development of effective targeted therapies for these ocular disorders will require a de- tailed understanding of the heterogeneity of ocular endothelia. Our review summarizes the existing literature relating to diversity of the ocular endothelial cells. We highlight structural, metabolic and functional characteristics that distinguish intraoocular endothelial subtypes from each other and from extraocular endothelial cells, and we consider the implications of these differences for the design of novel biological therapeutics for eye diseases.
{"title":"Ocular Vascular Endothelial Heterogeneity","authors":"Ashima Bhattacharjee, Justine R. Smith","doi":"10.2174/1567270000906010131","DOIUrl":"https://doi.org/10.2174/1567270000906010131","url":null,"abstract":"Endothelial cells form the lining of the vasculature. Despite the continuity of this layer throughout the body, endothelial cells exhibit remarkable heterogeneity in structure, molecular composition and activity: between sites; and in response to different exposures. One important consequence of endothelial diversity is the localized nature of many vascu- lar disorders. To date a limited number of studies have attempted to define unique phenotypic features of the different in- traocular endothelial subpopulations, which include the endothelial cells of vascular beds in the iris, the choroid and the retina. Differences that distinguish endothelial cells in the circulations of the choroid and the retina, in particular, are be- lieved to be major etiological factors controlling the specific involvement of the two tissues in some of the most common blinding diseases. Age-related macular degeneration involves choroid, and diabetic retinopathy and posterior uveitis are primarily diseases of the retina. Development of effective targeted therapies for these ocular disorders will require a de- tailed understanding of the heterogeneity of ocular endothelia. Our review summarizes the existing literature relating to diversity of the ocular endothelial cells. We highlight structural, metabolic and functional characteristics that distinguish intraoocular endothelial subtypes from each other and from extraocular endothelial cells, and we consider the implications of these differences for the design of novel biological therapeutics for eye diseases.","PeriodicalId":88793,"journal":{"name":"Vascular disease prevention","volume":"6 1","pages":"131-138"},"PeriodicalIF":0.0,"publicationDate":"2009-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67888871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-04-10DOI: 10.2174/1567270000906010114
B. Doyle, A. Callanan, M. Walsh, P. Grace, T. McGloughlin
Currently, abdominal aortic aneurysms (AAAs), which are a permanent dilation of the aorta, are treated surgi- cally when the maximum transverse diameter surpasses 5.5cm. AAA rupture occurs when the locally acting wall stress exceeds the locally acting wall strength. There is a need to review the current diameter-based criterion, and so it may be clinically useful to develop an additional tool to aid the surgical decision-making process. A Finite Element Analysis Rup- ture Index (FEARI) was developed. Ten patient-specific AAAs were reconstructed, and the corresponding wall stress computed. Previous experimental work on determination of ultimate tensile strengths (UTS) from AAA tissue samples was implemented in this study. By com- bining peak wall stress along with average regional UTS, a new approach to the estimation of patient-specific rupture risk has been developed. Ten cases were studied, all of which were awaiting or had previously undergone surgical AAA repair. A detailed exami- nation of these ten cases utilising the FEARI analysis suggested that there was a possibility that some of the AAAs may have been less prone to rupture than previously considered. It is proposed that FEARI, used alongside other rupture risk factors, may improve the current surgical decision-making process. The use of FEARI as an additional tool for rupture prediction may provide a useful adjunct to the diameter-based approach in surgical decision-making.
{"title":"A Finite Element Analysis Rupture Index (FEARI) as an Additional Tool for Abdominal Aortic Aneurysm Rupture Prediction","authors":"B. Doyle, A. Callanan, M. Walsh, P. Grace, T. McGloughlin","doi":"10.2174/1567270000906010114","DOIUrl":"https://doi.org/10.2174/1567270000906010114","url":null,"abstract":"Currently, abdominal aortic aneurysms (AAAs), which are a permanent dilation of the aorta, are treated surgi- cally when the maximum transverse diameter surpasses 5.5cm. AAA rupture occurs when the locally acting wall stress exceeds the locally acting wall strength. There is a need to review the current diameter-based criterion, and so it may be clinically useful to develop an additional tool to aid the surgical decision-making process. A Finite Element Analysis Rup- ture Index (FEARI) was developed. Ten patient-specific AAAs were reconstructed, and the corresponding wall stress computed. Previous experimental work on determination of ultimate tensile strengths (UTS) from AAA tissue samples was implemented in this study. By com- bining peak wall stress along with average regional UTS, a new approach to the estimation of patient-specific rupture risk has been developed. Ten cases were studied, all of which were awaiting or had previously undergone surgical AAA repair. A detailed exami- nation of these ten cases utilising the FEARI analysis suggested that there was a possibility that some of the AAAs may have been less prone to rupture than previously considered. It is proposed that FEARI, used alongside other rupture risk factors, may improve the current surgical decision-making process. The use of FEARI as an additional tool for rupture prediction may provide a useful adjunct to the diameter-based approach in surgical decision-making.","PeriodicalId":88793,"journal":{"name":"Vascular disease prevention","volume":"6 1","pages":"114-121"},"PeriodicalIF":0.0,"publicationDate":"2009-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67889000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-03-25DOI: 10.2174/1567270000906010109
S. Mendis
Scaling up research is essential to prevent and contain the rapidly growing epidemic of cardiovascular diseases (CVD) in low- and middle- income (LMIC) countries. Research funds are generally limited and need to be invested pri- marily to generate new knowledge on how to translate existing evidence into action and not for the discovery of novel causes and treatments. Problem-oriented health policy and systems research have a critical role to play in the effective im- plementation of a policy framework for addressing cardiovascular diseases. Research need to identify effective multistakeholder regulatory approaches that impact on diet, tobacco use and physical activity. Policy interventions that have the potential to reduce social gradient of major noncommunicable diseases (NCD) through the reduction of social stratification, vulnerability and exposure to risk factors also merit research. Macro and micro economic appraisals are re- quired to assess the economic impact of risks and diseases and cost effectiveness of different types of health interventions in different settings. Appropriate resource allocation for medical technology need to be researched in order to maximize health benefits and equity in low resource environments. Important modifiers of health system effectiveness such as ad- herence of patients and performance of providers also need to be studied. Further, the widening gap between the need for long-term care and the capacity of welfare programs to fulfill that need and the limited economic capacity of LMIC, calls for research into new public financing mechanisms to provide financial protection care. Finally, the research agenda need to be pro-poor so that the social gradient related to CVD can be narrowed to contribute to progress towards the Millen- nium Development Goals.
{"title":"The Need to Scale-Up Research for Prevention and Control of Cardiovascular Diseases","authors":"S. Mendis","doi":"10.2174/1567270000906010109","DOIUrl":"https://doi.org/10.2174/1567270000906010109","url":null,"abstract":"Scaling up research is essential to prevent and contain the rapidly growing epidemic of cardiovascular diseases (CVD) in low- and middle- income (LMIC) countries. Research funds are generally limited and need to be invested pri- marily to generate new knowledge on how to translate existing evidence into action and not for the discovery of novel causes and treatments. Problem-oriented health policy and systems research have a critical role to play in the effective im- plementation of a policy framework for addressing cardiovascular diseases. Research need to identify effective multistakeholder regulatory approaches that impact on diet, tobacco use and physical activity. Policy interventions that have the potential to reduce social gradient of major noncommunicable diseases (NCD) through the reduction of social stratification, vulnerability and exposure to risk factors also merit research. Macro and micro economic appraisals are re- quired to assess the economic impact of risks and diseases and cost effectiveness of different types of health interventions in different settings. Appropriate resource allocation for medical technology need to be researched in order to maximize health benefits and equity in low resource environments. Important modifiers of health system effectiveness such as ad- herence of patients and performance of providers also need to be studied. Further, the widening gap between the need for long-term care and the capacity of welfare programs to fulfill that need and the limited economic capacity of LMIC, calls for research into new public financing mechanisms to provide financial protection care. Finally, the research agenda need to be pro-poor so that the social gradient related to CVD can be narrowed to contribute to progress towards the Millen- nium Development Goals.","PeriodicalId":88793,"journal":{"name":"Vascular disease prevention","volume":"6 1","pages":"109-113"},"PeriodicalIF":0.0,"publicationDate":"2009-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67888985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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