Objective: To examine the expression and localisation of adrenomedullln in hum an coronary atherosclerotic lesions from patients with unstable angina(UAP) and stable angina(SAP), and to study the relation between adre...Objective: To examine the expression and localisation of adrenomedullln in hum an coronary atherosclerotic lesions from patients with unstable angina(UAP) and stable angina(SAP), and to study the relation between adrenomedullin expression and plaque instability. Design: A retrospective observational study. Patients: D irectional coronary atherectomy samples were obtained from 15 patients with UAP and 12 with SAP. Methods: The localisation of adrenomedullin was examined by imm unohistochemistry, and adrenomedullin mRNA expression was measured by quantitati ve polymerase chain reaction. Results: Adrenomedullin immunoreactivity was prefe rentially localised in macrophages, intimai smooth muscle cells, and proliferate d microvessels. The mean number of adrenomedullin positive cells in five high po wer fields(x 400) per specimen was higher in patients with UAP than in those wit h SAP (mean (SEM), 110(13) v 76 (7); p< 0.05); and the ratio of adrenomedullin p ositive to total cells was higher in patients with UAP (43.0 (2.2)%v 34.2 (2.0) %; p< 0.01). More adrenomedullin mRNA was expressed in the plaque of patients w ith UAP than in those with SAP (60.4 (16.9)%v 9.7 (3.3)%; p< 0.01). Conclusion s: The findings suggest that adrenomedullin is involved in the development of at herosclerosis and plaque instability in human coronary arteries, in an autocrine or paracrine manner.展开更多
Objective: The impairment of the tissue kallikrein- kinin system(KKS) may result in atheroma development. To determine the involvement of KKS in pathophysiology of human atherosclerosis, we examined the expression of ...Objective: The impairment of the tissue kallikrein- kinin system(KKS) may result in atheroma development. To determine the involvement of KKS in pathophysiology of human atherosclerosis, we examined the expression of all components of this system as well as angiotensinogen(another tissue kallikrein(TK) substrate), at messenger ribonucleic acid(mRNA) and protein levels in the human carotid artery with and without atheroma. Methods: mRNA levels were compared with semiquantitative reverse transcriptase- polymerase chain reaction(RT- PCR) between atheroma plaque and intact tissue obtained during carotid endarterectomy in 15 patients. The cellular localization of the transcripts and proteins was analyzed with in situ hybridization and immunohistochemistry. TK activity was measured using chromogenic substrate. Results: The kininogen mRNA was not detected in carotid wall. The TK mRNA was increased four- fold and TK activity 23- fold in atheroma plaque compared with intact tissue. No difference was observed for B1, B2 receptors, kallistatin, angiotensinogen and protein- kinase G type 1α (PK- G) mRNAs. The TK and angiotensinogen transcripts as well as kininogen and angiotensinogen proteins were present in both intimal and medial cells. The kininogen immunoreactivity was weaker in atheroma. Conclusions: All KKS components were synthesized in arterial wall except kininogen probably coming from plasma. The absence of PK- G mRNA down- regulation in atheroma suggests that the kallikrein induction does not lead to KKS activation.展开更多
文摘Objective: To examine the expression and localisation of adrenomedullln in hum an coronary atherosclerotic lesions from patients with unstable angina(UAP) and stable angina(SAP), and to study the relation between adrenomedullin expression and plaque instability. Design: A retrospective observational study. Patients: D irectional coronary atherectomy samples were obtained from 15 patients with UAP and 12 with SAP. Methods: The localisation of adrenomedullin was examined by imm unohistochemistry, and adrenomedullin mRNA expression was measured by quantitati ve polymerase chain reaction. Results: Adrenomedullin immunoreactivity was prefe rentially localised in macrophages, intimai smooth muscle cells, and proliferate d microvessels. The mean number of adrenomedullin positive cells in five high po wer fields(x 400) per specimen was higher in patients with UAP than in those wit h SAP (mean (SEM), 110(13) v 76 (7); p< 0.05); and the ratio of adrenomedullin p ositive to total cells was higher in patients with UAP (43.0 (2.2)%v 34.2 (2.0) %; p< 0.01). More adrenomedullin mRNA was expressed in the plaque of patients w ith UAP than in those with SAP (60.4 (16.9)%v 9.7 (3.3)%; p< 0.01). Conclusion s: The findings suggest that adrenomedullin is involved in the development of at herosclerosis and plaque instability in human coronary arteries, in an autocrine or paracrine manner.
文摘Objective: The impairment of the tissue kallikrein- kinin system(KKS) may result in atheroma development. To determine the involvement of KKS in pathophysiology of human atherosclerosis, we examined the expression of all components of this system as well as angiotensinogen(another tissue kallikrein(TK) substrate), at messenger ribonucleic acid(mRNA) and protein levels in the human carotid artery with and without atheroma. Methods: mRNA levels were compared with semiquantitative reverse transcriptase- polymerase chain reaction(RT- PCR) between atheroma plaque and intact tissue obtained during carotid endarterectomy in 15 patients. The cellular localization of the transcripts and proteins was analyzed with in situ hybridization and immunohistochemistry. TK activity was measured using chromogenic substrate. Results: The kininogen mRNA was not detected in carotid wall. The TK mRNA was increased four- fold and TK activity 23- fold in atheroma plaque compared with intact tissue. No difference was observed for B1, B2 receptors, kallistatin, angiotensinogen and protein- kinase G type 1α (PK- G) mRNAs. The TK and angiotensinogen transcripts as well as kininogen and angiotensinogen proteins were present in both intimal and medial cells. The kininogen immunoreactivity was weaker in atheroma. Conclusions: All KKS components were synthesized in arterial wall except kininogen probably coming from plasma. The absence of PK- G mRNA down- regulation in atheroma suggests that the kallikrein induction does not lead to KKS activation.
