Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-...Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-terol from peripheral tissue to liver which has several potent antiatherogenic properties. For instance, the particles of HDL mediate to transport cholesterol from cells in arterial tissues, particularly from atherosclerotic plaques, to the liver. Both ATP-binding cassette trans-porters(ABC) A1 and ABCG1 are membrane cholesterol transporters and have been implicated in mediating cholesterol effluxes from cells in the presence of HDL and apolipoprotein A-I, a major protein constituent of HDL. Previous studies demonstrated that ABCA1 and ABCG1 or the interaction between ABCA1 and ABCG1 exerted antiatherosclerotic effects. As a therapeutic approach for increasing HDL cholesterol levels, much focus has been placed on increasing HDL cholesterol levels as well as enhancing HDL biochemical functions. HDL therapies that use injections of reconstituted HDL, apoA-I mimetics, or full-length apoA-I have shown dramatic effectiveness. In particular, a novel apoA-I mi-metic peptide, Fukuoka University ApoA-I Mimetic Pep-tide, effectively removes cholesterol via specific ABCA1 and other transporters, such as ABCG1, and has an an-tiatherosclerotic effect by enhancing the biological func-tions of HDL without changing circulating HDL choles-terol levels. Thus, HDL-targeting therapy has significant atheroprotective potential, as it uses lipid transporter-targeting agents, and may prove to be a therapeutic tool for atherosclerotic cardiovascular diseases.展开更多
AIM: To evaluate the role of chymase in blood pressure regulation and its actions on tissue renin-angiotensin system.METHODS: A two-kidney, one-clip(2K1C) hypertension model was developed in Syrian hamsters, which hav...AIM: To evaluate the role of chymase in blood pressure regulation and its actions on tissue renin-angiotensin system.METHODS: A two-kidney, one-clip(2K1C) hypertension model was developed in Syrian hamsters, which have a human-type chymase. Either an angiotensin(Ang) converting enzyme(ACE) inhibitor(ACE-I; temocapril, 30 mg/kg per day), Ang Ⅱ type 1 receptor antagonist(ARB; CS866, 10 mg/kg per day), or vehicle was administered, beginning 2 wk after renal artery clipping and continued for 16 wk. At the end of this protocol, hearts, aortas, and lungs were removed, and total Ang Ⅱ-forming activities and ACE- and chymasedependent Ang Ⅱ-forming activities were determined.RESULTS: After renal artery clipping, systolic blood pressure in the vehicle group was significantly higher compared with that in a sham-operated group throughoutthe experimental period. Both ACE-I and ARB treatments revealed similar antihypertensive effects. Moreover, in the vehicle group, cardiac total and chymase-dependent Ang Ⅱ-forming activities significantly increased at 18 wk after clipping. Further, cardiac total and chymase-dependent Ang Ⅱ-forming activities decreased significantly after ACE-I or ARB treatment for 16 wk. In addition, chymase-dependent Ang Ⅱ-forming activity significantly increased in the aorta, although these changes were inhibited only by ARB. ARB treatment was more effective compared with ACE-I treatment in reversing the changes in tissue Ang Ⅱ formation, particularly in the aorta, despite their similar antihypertensive effects.CONCLUSION: Chymase does not play a major role in maintaining blood pressure and tissue ACE and chymase are regulated in a tissue-dependent manner in 2K1 C hamster.展开更多
文摘Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-terol from peripheral tissue to liver which has several potent antiatherogenic properties. For instance, the particles of HDL mediate to transport cholesterol from cells in arterial tissues, particularly from atherosclerotic plaques, to the liver. Both ATP-binding cassette trans-porters(ABC) A1 and ABCG1 are membrane cholesterol transporters and have been implicated in mediating cholesterol effluxes from cells in the presence of HDL and apolipoprotein A-I, a major protein constituent of HDL. Previous studies demonstrated that ABCA1 and ABCG1 or the interaction between ABCA1 and ABCG1 exerted antiatherosclerotic effects. As a therapeutic approach for increasing HDL cholesterol levels, much focus has been placed on increasing HDL cholesterol levels as well as enhancing HDL biochemical functions. HDL therapies that use injections of reconstituted HDL, apoA-I mimetics, or full-length apoA-I have shown dramatic effectiveness. In particular, a novel apoA-I mi-metic peptide, Fukuoka University ApoA-I Mimetic Pep-tide, effectively removes cholesterol via specific ABCA1 and other transporters, such as ABCG1, and has an an-tiatherosclerotic effect by enhancing the biological func-tions of HDL without changing circulating HDL choles-terol levels. Thus, HDL-targeting therapy has significant atheroprotective potential, as it uses lipid transporter-targeting agents, and may prove to be a therapeutic tool for atherosclerotic cardiovascular diseases.
文摘AIM: To evaluate the role of chymase in blood pressure regulation and its actions on tissue renin-angiotensin system.METHODS: A two-kidney, one-clip(2K1C) hypertension model was developed in Syrian hamsters, which have a human-type chymase. Either an angiotensin(Ang) converting enzyme(ACE) inhibitor(ACE-I; temocapril, 30 mg/kg per day), Ang Ⅱ type 1 receptor antagonist(ARB; CS866, 10 mg/kg per day), or vehicle was administered, beginning 2 wk after renal artery clipping and continued for 16 wk. At the end of this protocol, hearts, aortas, and lungs were removed, and total Ang Ⅱ-forming activities and ACE- and chymasedependent Ang Ⅱ-forming activities were determined.RESULTS: After renal artery clipping, systolic blood pressure in the vehicle group was significantly higher compared with that in a sham-operated group throughoutthe experimental period. Both ACE-I and ARB treatments revealed similar antihypertensive effects. Moreover, in the vehicle group, cardiac total and chymase-dependent Ang Ⅱ-forming activities significantly increased at 18 wk after clipping. Further, cardiac total and chymase-dependent Ang Ⅱ-forming activities decreased significantly after ACE-I or ARB treatment for 16 wk. In addition, chymase-dependent Ang Ⅱ-forming activity significantly increased in the aorta, although these changes were inhibited only by ARB. ARB treatment was more effective compared with ACE-I treatment in reversing the changes in tissue Ang Ⅱ formation, particularly in the aorta, despite their similar antihypertensive effects.CONCLUSION: Chymase does not play a major role in maintaining blood pressure and tissue ACE and chymase are regulated in a tissue-dependent manner in 2K1 C hamster.
