The Experts below are selected from a list of 39 Experts worldwide ranked by ideXlab platform

Sergei M. Danilov - One of the best experts on this subject based on the ideXlab platform.

  • Conformational Changes of Blood ACE in Chronic Uremia
    2016
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, R V. Tarasov, Sergei M. Danilov
    Abstract:

    Background: The pattern of binding of monoclonal antibodies (mAbs) to 16 epitopes on human angiotensin I-converting enzyme (ACE) comprise a conformational ACE fingerprint and is a sensitive marker of subtle protein conformational changes. Hypothesis: Toxic substances in the blood of patients with uremia due to End Stage Renal Disease (ESRD) can induce local conformational changes in the ACE protein globule and alter the efficacy of ACE inhibitors. Methodology/Principal Findings: The recognition of ACE by 16 mAbs to the epitopes on the N and C domains of ACE was estimated using an immune-capture enzymatic plate precipitation assay. The precipitation pattern of blood ACE by a set of mAbs was substantially influenced by the presence of ACE inhibitors with the most dramatic local conformational change noted in the N-domain region recognized by mAb 1G12. The ‘‘short’ ’ ACE inhibitor enalaprilat (tripeptide analog) and ‘‘long’’ inhibitor Teprotide (nonapeptide) produced strikingly different mAb 1G12 binding with enalaprilat strongly increasing mAb 1G12 binding and Teprotide decreasing binding. Reduction in S-S bonds via glutathione and dithiothreitol treatment increased 1G12 binding to blood ACE in a manner comparable to enalaprilat. Some patients with uremia due to ESRD exhibited significantly increased mAb 1G12 binding to blood ACE and increased ACE activity towards angiotensin I accompanied by reduced ACE inhibition by inhibitory mAbs and ACE inhibitors

  • Effect of ACE inhibitors on blood ACE activity.
    2014
    Co-Authors: Sergei M. Danilov, David E. Schwartz, Michael S. Wade, Sylva L. Schwager, Ross G. Douglas, Andrew B. Nesterovitch, Isolda A. Popova, Kyle D. Hogarth, Nakul Bhardwaj, Edward D. Sturrock
    Abstract:

    Serum samples (1/5 dilution in PBS) from pool of 10 healthy volunteers (control) and from patient # 27 (arrowed in Fig. 1 C) were incubated with different concentration of ACE inhibitors: short –enalaprilat (A) and long –Teprotide (B). Residual ACE activity was determined with two ACE substrates (and ZPHL/HHL ratio) as in Fig. 2. Data presented are mean ± SD of 2–3 independent experiments in duplicates). * p

  • Conformational Changes of Blood ACE in Chronic Uremia
    PloS one, 2012
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, Alexandr V. Tarasov, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, Sergei M. Danilov
    Abstract:

    Background: The pattern of binding of monoclonal antibodies (mAbs) to 16 epitopes on human angiotensin I-converting enzyme (ACE) comprise a conformational ACE fingerprint and is a sensitive marker of subtle protein conformational changes. Hypothesis: Toxic substances in the blood of patients with uremia due to End Stage Renal Disease (ESRD) can induce local conformational changes in the ACE protein globule and alter the efficacy of ACE inhibitors. Methodology/Principal Findings: The recognition of ACE by 16 mAbs to the epitopes on the N and C domains of ACE was estimated using an immune-capture enzymatic plate precipitation assay. The precipitation pattern of blood ACE by a set of mAbs was substantially influenced by the presence of ACE inhibitors with the most dramatic local conformational change noted in the N-domain region recognized by mAb 1G12. The ‘‘short’’ ACE inhibitor enalaprilat (tripeptide analog) and ‘‘long’’ inhibitor Teprotide (nonapeptide) produced strikingly different mAb 1G12 binding with enalaprilat strongly increasing mAb 1G12 binding and Teprotide decreasing binding. Reduction in S-S bonds via glutathione and dithiothreitol treatment increased 1G12 binding to blood ACE in a manner comparable to enalaprilat. Some patients with uremia due to ESRD exhibited significantly increased mAb 1G12 binding to blood ACE and increased ACE activity towards angiotensin I accompanied by reduced ACE inhibition by inhibitory mAbs and ACE inhibitors. Conclusions/Significance: The estimation of relative mAb 1G12 binding to blood ACE detects a subpopulation of ESRD patients with conformationally changed ACE, which activity is less suppressible by ACE inhibitors. This parameter may potentially serve as a biomarker for those patients who may need higher concentrations of ACE inhibitors upon antihypertensive therapy.

  • Effect of ACE inhibitors on the local conformation of blood ACE in uremia.
    2012
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, Alexandr V. Tarasov, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, Sergei M. Danilov
    Abstract:

    A. The ratio of ACE activities precipitated from the citrated plasma of uremic patients by mAbs 1G12 and 9B9 (1G12/9B9 ratio) and from pooled plasma from healthy volunteers in the presence of enalaprilat (100 nM) – red bars and without the inhibitor – grey bars. B. The data presented on Fig. 5A were also expressed as a percentage of the effect of enalaprilat on the values of 1G12/9B9 ratio for different patients. The red columns show those mAbs for which enalaprilat effect (increase of mAb binding) exceeded 20%. C. The ratio of ACE activities precipitated from the citrated plasma of uremic patients by mAbs 1G12 and 9B9 (1G12/9B9 ratio) and from pooled plasma from healthy volunteers in the presence of Teprotide (1 µM) – blue bars and without the inhibitor – grey bars. D. The data presented on Fig. 5C were also expressed as a percentage of the effect of Teprotide on the values of 1G12/9B9 ratio for different patients. The yellow columns show those mAbs for which Teprotide effect (decrease of mAb binding) exceeded 20%. All other terms and conditions – as in Figure 1. Data are mean ± SD of 3 independent experiments (each in duplicates). *, p

  • Effect of ACE inhibitors on the activity of plasma ACE in uremia.
    2012
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, Alexandr V. Tarasov, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, Sergei M. Danilov
    Abstract:

    A–D Citrated plasma samples of uremic patients with normal (patients #14 and #2) and high (patients #11 and #13) 1G12/9B9 ratio (versus healthy controls, #11 and #19) were incubated with “short” ACE inhibitor enalaprilat (100 nM, A and B) and “long” ACE inhibitor Teprotide (1 µM, C and D) for 1 hour. Data are presented as a residual ACE activity determined with “short” substrate ZPHL (0.5 mM, A and C) and “long” substrate angiotensin I (0.3 mM, B and D). Data are presented as a residual ACE activity. E. The ratio of the rates of the hydrolysis of angiotensin I and ZPHL (angiotensin I/ZPHL ratio) for corresponding samples. F. mAb1G12/9B9 binding ratio for corresponding samples expressed as % from the mean value for healthy persons. Grey bars – inhibition of ACE activity (A–D) or parameters measured in E–F in uremic samples was not differed from that for healthy patients with low 1G12/9B9 ratio. Red bars –measured parameters were statistically higher than that in healthy patients with low (normal) 1G12/9B9 ratio *, p

Maxim N. Petrov - One of the best experts on this subject based on the ideXlab platform.

  • Conformational Changes of Blood ACE in Chronic Uremia
    2016
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, R V. Tarasov, Sergei M. Danilov
    Abstract:

    Background: The pattern of binding of monoclonal antibodies (mAbs) to 16 epitopes on human angiotensin I-converting enzyme (ACE) comprise a conformational ACE fingerprint and is a sensitive marker of subtle protein conformational changes. Hypothesis: Toxic substances in the blood of patients with uremia due to End Stage Renal Disease (ESRD) can induce local conformational changes in the ACE protein globule and alter the efficacy of ACE inhibitors. Methodology/Principal Findings: The recognition of ACE by 16 mAbs to the epitopes on the N and C domains of ACE was estimated using an immune-capture enzymatic plate precipitation assay. The precipitation pattern of blood ACE by a set of mAbs was substantially influenced by the presence of ACE inhibitors with the most dramatic local conformational change noted in the N-domain region recognized by mAb 1G12. The ‘‘short’ ’ ACE inhibitor enalaprilat (tripeptide analog) and ‘‘long’’ inhibitor Teprotide (nonapeptide) produced strikingly different mAb 1G12 binding with enalaprilat strongly increasing mAb 1G12 binding and Teprotide decreasing binding. Reduction in S-S bonds via glutathione and dithiothreitol treatment increased 1G12 binding to blood ACE in a manner comparable to enalaprilat. Some patients with uremia due to ESRD exhibited significantly increased mAb 1G12 binding to blood ACE and increased ACE activity towards angiotensin I accompanied by reduced ACE inhibition by inhibitory mAbs and ACE inhibitors

  • Conformational Changes of Blood ACE in Chronic Uremia
    PloS one, 2012
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, Alexandr V. Tarasov, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, Sergei M. Danilov
    Abstract:

    Background: The pattern of binding of monoclonal antibodies (mAbs) to 16 epitopes on human angiotensin I-converting enzyme (ACE) comprise a conformational ACE fingerprint and is a sensitive marker of subtle protein conformational changes. Hypothesis: Toxic substances in the blood of patients with uremia due to End Stage Renal Disease (ESRD) can induce local conformational changes in the ACE protein globule and alter the efficacy of ACE inhibitors. Methodology/Principal Findings: The recognition of ACE by 16 mAbs to the epitopes on the N and C domains of ACE was estimated using an immune-capture enzymatic plate precipitation assay. The precipitation pattern of blood ACE by a set of mAbs was substantially influenced by the presence of ACE inhibitors with the most dramatic local conformational change noted in the N-domain region recognized by mAb 1G12. The ‘‘short’’ ACE inhibitor enalaprilat (tripeptide analog) and ‘‘long’’ inhibitor Teprotide (nonapeptide) produced strikingly different mAb 1G12 binding with enalaprilat strongly increasing mAb 1G12 binding and Teprotide decreasing binding. Reduction in S-S bonds via glutathione and dithiothreitol treatment increased 1G12 binding to blood ACE in a manner comparable to enalaprilat. Some patients with uremia due to ESRD exhibited significantly increased mAb 1G12 binding to blood ACE and increased ACE activity towards angiotensin I accompanied by reduced ACE inhibition by inhibitory mAbs and ACE inhibitors. Conclusions/Significance: The estimation of relative mAb 1G12 binding to blood ACE detects a subpopulation of ESRD patients with conformationally changed ACE, which activity is less suppressible by ACE inhibitors. This parameter may potentially serve as a biomarker for those patients who may need higher concentrations of ACE inhibitors upon antihypertensive therapy.

  • Effect of ACE inhibitors on the local conformation of blood ACE in uremia.
    2012
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, Alexandr V. Tarasov, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, Sergei M. Danilov
    Abstract:

    A. The ratio of ACE activities precipitated from the citrated plasma of uremic patients by mAbs 1G12 and 9B9 (1G12/9B9 ratio) and from pooled plasma from healthy volunteers in the presence of enalaprilat (100 nM) – red bars and without the inhibitor – grey bars. B. The data presented on Fig. 5A were also expressed as a percentage of the effect of enalaprilat on the values of 1G12/9B9 ratio for different patients. The red columns show those mAbs for which enalaprilat effect (increase of mAb binding) exceeded 20%. C. The ratio of ACE activities precipitated from the citrated plasma of uremic patients by mAbs 1G12 and 9B9 (1G12/9B9 ratio) and from pooled plasma from healthy volunteers in the presence of Teprotide (1 µM) – blue bars and without the inhibitor – grey bars. D. The data presented on Fig. 5C were also expressed as a percentage of the effect of Teprotide on the values of 1G12/9B9 ratio for different patients. The yellow columns show those mAbs for which Teprotide effect (decrease of mAb binding) exceeded 20%. All other terms and conditions – as in Figure 1. Data are mean ± SD of 3 independent experiments (each in duplicates). *, p

  • Effect of ACE inhibitors on the activity of plasma ACE in uremia.
    2012
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, Alexandr V. Tarasov, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, Sergei M. Danilov
    Abstract:

    A–D Citrated plasma samples of uremic patients with normal (patients #14 and #2) and high (patients #11 and #13) 1G12/9B9 ratio (versus healthy controls, #11 and #19) were incubated with “short” ACE inhibitor enalaprilat (100 nM, A and B) and “long” ACE inhibitor Teprotide (1 µM, C and D) for 1 hour. Data are presented as a residual ACE activity determined with “short” substrate ZPHL (0.5 mM, A and C) and “long” substrate angiotensin I (0.3 mM, B and D). Data are presented as a residual ACE activity. E. The ratio of the rates of the hydrolysis of angiotensin I and ZPHL (angiotensin I/ZPHL ratio) for corresponding samples. F. mAb1G12/9B9 binding ratio for corresponding samples expressed as % from the mean value for healthy persons. Grey bars – inhibition of ACE activity (A–D) or parameters measured in E–F in uremic samples was not differed from that for healthy patients with low 1G12/9B9 ratio. Red bars –measured parameters were statistically higher than that in healthy patients with low (normal) 1G12/9B9 ratio *, p

David E. Schwartz - One of the best experts on this subject based on the ideXlab platform.

  • Conformational Changes of Blood ACE in Chronic Uremia
    2016
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, R V. Tarasov, Sergei M. Danilov
    Abstract:

    Background: The pattern of binding of monoclonal antibodies (mAbs) to 16 epitopes on human angiotensin I-converting enzyme (ACE) comprise a conformational ACE fingerprint and is a sensitive marker of subtle protein conformational changes. Hypothesis: Toxic substances in the blood of patients with uremia due to End Stage Renal Disease (ESRD) can induce local conformational changes in the ACE protein globule and alter the efficacy of ACE inhibitors. Methodology/Principal Findings: The recognition of ACE by 16 mAbs to the epitopes on the N and C domains of ACE was estimated using an immune-capture enzymatic plate precipitation assay. The precipitation pattern of blood ACE by a set of mAbs was substantially influenced by the presence of ACE inhibitors with the most dramatic local conformational change noted in the N-domain region recognized by mAb 1G12. The ‘‘short’ ’ ACE inhibitor enalaprilat (tripeptide analog) and ‘‘long’’ inhibitor Teprotide (nonapeptide) produced strikingly different mAb 1G12 binding with enalaprilat strongly increasing mAb 1G12 binding and Teprotide decreasing binding. Reduction in S-S bonds via glutathione and dithiothreitol treatment increased 1G12 binding to blood ACE in a manner comparable to enalaprilat. Some patients with uremia due to ESRD exhibited significantly increased mAb 1G12 binding to blood ACE and increased ACE activity towards angiotensin I accompanied by reduced ACE inhibition by inhibitory mAbs and ACE inhibitors

  • Effect of ACE inhibitors on blood ACE activity.
    2014
    Co-Authors: Sergei M. Danilov, David E. Schwartz, Michael S. Wade, Sylva L. Schwager, Ross G. Douglas, Andrew B. Nesterovitch, Isolda A. Popova, Kyle D. Hogarth, Nakul Bhardwaj, Edward D. Sturrock
    Abstract:

    Serum samples (1/5 dilution in PBS) from pool of 10 healthy volunteers (control) and from patient # 27 (arrowed in Fig. 1 C) were incubated with different concentration of ACE inhibitors: short –enalaprilat (A) and long –Teprotide (B). Residual ACE activity was determined with two ACE substrates (and ZPHL/HHL ratio) as in Fig. 2. Data presented are mean ± SD of 2–3 independent experiments in duplicates). * p

  • Conformational Changes of Blood ACE in Chronic Uremia
    PloS one, 2012
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, Alexandr V. Tarasov, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, Sergei M. Danilov
    Abstract:

    Background: The pattern of binding of monoclonal antibodies (mAbs) to 16 epitopes on human angiotensin I-converting enzyme (ACE) comprise a conformational ACE fingerprint and is a sensitive marker of subtle protein conformational changes. Hypothesis: Toxic substances in the blood of patients with uremia due to End Stage Renal Disease (ESRD) can induce local conformational changes in the ACE protein globule and alter the efficacy of ACE inhibitors. Methodology/Principal Findings: The recognition of ACE by 16 mAbs to the epitopes on the N and C domains of ACE was estimated using an immune-capture enzymatic plate precipitation assay. The precipitation pattern of blood ACE by a set of mAbs was substantially influenced by the presence of ACE inhibitors with the most dramatic local conformational change noted in the N-domain region recognized by mAb 1G12. The ‘‘short’’ ACE inhibitor enalaprilat (tripeptide analog) and ‘‘long’’ inhibitor Teprotide (nonapeptide) produced strikingly different mAb 1G12 binding with enalaprilat strongly increasing mAb 1G12 binding and Teprotide decreasing binding. Reduction in S-S bonds via glutathione and dithiothreitol treatment increased 1G12 binding to blood ACE in a manner comparable to enalaprilat. Some patients with uremia due to ESRD exhibited significantly increased mAb 1G12 binding to blood ACE and increased ACE activity towards angiotensin I accompanied by reduced ACE inhibition by inhibitory mAbs and ACE inhibitors. Conclusions/Significance: The estimation of relative mAb 1G12 binding to blood ACE detects a subpopulation of ESRD patients with conformationally changed ACE, which activity is less suppressible by ACE inhibitors. This parameter may potentially serve as a biomarker for those patients who may need higher concentrations of ACE inhibitors upon antihypertensive therapy.

  • Effect of ACE inhibitors on the local conformation of blood ACE in uremia.
    2012
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, Alexandr V. Tarasov, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, Sergei M. Danilov
    Abstract:

    A. The ratio of ACE activities precipitated from the citrated plasma of uremic patients by mAbs 1G12 and 9B9 (1G12/9B9 ratio) and from pooled plasma from healthy volunteers in the presence of enalaprilat (100 nM) – red bars and without the inhibitor – grey bars. B. The data presented on Fig. 5A were also expressed as a percentage of the effect of enalaprilat on the values of 1G12/9B9 ratio for different patients. The red columns show those mAbs for which enalaprilat effect (increase of mAb binding) exceeded 20%. C. The ratio of ACE activities precipitated from the citrated plasma of uremic patients by mAbs 1G12 and 9B9 (1G12/9B9 ratio) and from pooled plasma from healthy volunteers in the presence of Teprotide (1 µM) – blue bars and without the inhibitor – grey bars. D. The data presented on Fig. 5C were also expressed as a percentage of the effect of Teprotide on the values of 1G12/9B9 ratio for different patients. The yellow columns show those mAbs for which Teprotide effect (decrease of mAb binding) exceeded 20%. All other terms and conditions – as in Figure 1. Data are mean ± SD of 3 independent experiments (each in duplicates). *, p

  • Effect of ACE inhibitors on the activity of plasma ACE in uremia.
    2012
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, Alexandr V. Tarasov, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, Sergei M. Danilov
    Abstract:

    A–D Citrated plasma samples of uremic patients with normal (patients #14 and #2) and high (patients #11 and #13) 1G12/9B9 ratio (versus healthy controls, #11 and #19) were incubated with “short” ACE inhibitor enalaprilat (100 nM, A and B) and “long” ACE inhibitor Teprotide (1 µM, C and D) for 1 hour. Data are presented as a residual ACE activity determined with “short” substrate ZPHL (0.5 mM, A and C) and “long” substrate angiotensin I (0.3 mM, B and D). Data are presented as a residual ACE activity. E. The ratio of the rates of the hydrolysis of angiotensin I and ZPHL (angiotensin I/ZPHL ratio) for corresponding samples. F. mAb1G12/9B9 binding ratio for corresponding samples expressed as % from the mean value for healthy persons. Grey bars – inhibition of ACE activity (A–D) or parameters measured in E–F in uremic samples was not differed from that for healthy patients with low 1G12/9B9 ratio. Red bars –measured parameters were statistically higher than that in healthy patients with low (normal) 1G12/9B9 ratio *, p

Joe G. N. Garcia - One of the best experts on this subject based on the ideXlab platform.

  • Conformational Changes of Blood ACE in Chronic Uremia
    2016
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, R V. Tarasov, Sergei M. Danilov
    Abstract:

    Background: The pattern of binding of monoclonal antibodies (mAbs) to 16 epitopes on human angiotensin I-converting enzyme (ACE) comprise a conformational ACE fingerprint and is a sensitive marker of subtle protein conformational changes. Hypothesis: Toxic substances in the blood of patients with uremia due to End Stage Renal Disease (ESRD) can induce local conformational changes in the ACE protein globule and alter the efficacy of ACE inhibitors. Methodology/Principal Findings: The recognition of ACE by 16 mAbs to the epitopes on the N and C domains of ACE was estimated using an immune-capture enzymatic plate precipitation assay. The precipitation pattern of blood ACE by a set of mAbs was substantially influenced by the presence of ACE inhibitors with the most dramatic local conformational change noted in the N-domain region recognized by mAb 1G12. The ‘‘short’ ’ ACE inhibitor enalaprilat (tripeptide analog) and ‘‘long’’ inhibitor Teprotide (nonapeptide) produced strikingly different mAb 1G12 binding with enalaprilat strongly increasing mAb 1G12 binding and Teprotide decreasing binding. Reduction in S-S bonds via glutathione and dithiothreitol treatment increased 1G12 binding to blood ACE in a manner comparable to enalaprilat. Some patients with uremia due to ESRD exhibited significantly increased mAb 1G12 binding to blood ACE and increased ACE activity towards angiotensin I accompanied by reduced ACE inhibition by inhibitory mAbs and ACE inhibitors

  • Conformational Changes of Blood ACE in Chronic Uremia
    PloS one, 2012
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, Alexandr V. Tarasov, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, Sergei M. Danilov
    Abstract:

    Background: The pattern of binding of monoclonal antibodies (mAbs) to 16 epitopes on human angiotensin I-converting enzyme (ACE) comprise a conformational ACE fingerprint and is a sensitive marker of subtle protein conformational changes. Hypothesis: Toxic substances in the blood of patients with uremia due to End Stage Renal Disease (ESRD) can induce local conformational changes in the ACE protein globule and alter the efficacy of ACE inhibitors. Methodology/Principal Findings: The recognition of ACE by 16 mAbs to the epitopes on the N and C domains of ACE was estimated using an immune-capture enzymatic plate precipitation assay. The precipitation pattern of blood ACE by a set of mAbs was substantially influenced by the presence of ACE inhibitors with the most dramatic local conformational change noted in the N-domain region recognized by mAb 1G12. The ‘‘short’’ ACE inhibitor enalaprilat (tripeptide analog) and ‘‘long’’ inhibitor Teprotide (nonapeptide) produced strikingly different mAb 1G12 binding with enalaprilat strongly increasing mAb 1G12 binding and Teprotide decreasing binding. Reduction in S-S bonds via glutathione and dithiothreitol treatment increased 1G12 binding to blood ACE in a manner comparable to enalaprilat. Some patients with uremia due to ESRD exhibited significantly increased mAb 1G12 binding to blood ACE and increased ACE activity towards angiotensin I accompanied by reduced ACE inhibition by inhibitory mAbs and ACE inhibitors. Conclusions/Significance: The estimation of relative mAb 1G12 binding to blood ACE detects a subpopulation of ESRD patients with conformationally changed ACE, which activity is less suppressible by ACE inhibitors. This parameter may potentially serve as a biomarker for those patients who may need higher concentrations of ACE inhibitors upon antihypertensive therapy.

  • Effect of ACE inhibitors on the local conformation of blood ACE in uremia.
    2012
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, Alexandr V. Tarasov, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, Sergei M. Danilov
    Abstract:

    A. The ratio of ACE activities precipitated from the citrated plasma of uremic patients by mAbs 1G12 and 9B9 (1G12/9B9 ratio) and from pooled plasma from healthy volunteers in the presence of enalaprilat (100 nM) – red bars and without the inhibitor – grey bars. B. The data presented on Fig. 5A were also expressed as a percentage of the effect of enalaprilat on the values of 1G12/9B9 ratio for different patients. The red columns show those mAbs for which enalaprilat effect (increase of mAb binding) exceeded 20%. C. The ratio of ACE activities precipitated from the citrated plasma of uremic patients by mAbs 1G12 and 9B9 (1G12/9B9 ratio) and from pooled plasma from healthy volunteers in the presence of Teprotide (1 µM) – blue bars and without the inhibitor – grey bars. D. The data presented on Fig. 5C were also expressed as a percentage of the effect of Teprotide on the values of 1G12/9B9 ratio for different patients. The yellow columns show those mAbs for which Teprotide effect (decrease of mAb binding) exceeded 20%. All other terms and conditions – as in Figure 1. Data are mean ± SD of 3 independent experiments (each in duplicates). *, p

  • Effect of ACE inhibitors on the activity of plasma ACE in uremia.
    2012
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, Alexandr V. Tarasov, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, Sergei M. Danilov
    Abstract:

    A–D Citrated plasma samples of uremic patients with normal (patients #14 and #2) and high (patients #11 and #13) 1G12/9B9 ratio (versus healthy controls, #11 and #19) were incubated with “short” ACE inhibitor enalaprilat (100 nM, A and B) and “long” ACE inhibitor Teprotide (1 µM, C and D) for 1 hour. Data are presented as a residual ACE activity determined with “short” substrate ZPHL (0.5 mM, A and C) and “long” substrate angiotensin I (0.3 mM, B and D). Data are presented as a residual ACE activity. E. The ratio of the rates of the hydrolysis of angiotensin I and ZPHL (angiotensin I/ZPHL ratio) for corresponding samples. F. mAb1G12/9B9 binding ratio for corresponding samples expressed as % from the mean value for healthy persons. Grey bars – inhibition of ACE activity (A–D) or parameters measured in E–F in uremic samples was not differed from that for healthy patients with low 1G12/9B9 ratio. Red bars –measured parameters were statistically higher than that in healthy patients with low (normal) 1G12/9B9 ratio *, p

Olga A. Kost - One of the best experts on this subject based on the ideXlab platform.

  • Conformational Changes of Blood ACE in Chronic Uremia
    2016
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, R V. Tarasov, Sergei M. Danilov
    Abstract:

    Background: The pattern of binding of monoclonal antibodies (mAbs) to 16 epitopes on human angiotensin I-converting enzyme (ACE) comprise a conformational ACE fingerprint and is a sensitive marker of subtle protein conformational changes. Hypothesis: Toxic substances in the blood of patients with uremia due to End Stage Renal Disease (ESRD) can induce local conformational changes in the ACE protein globule and alter the efficacy of ACE inhibitors. Methodology/Principal Findings: The recognition of ACE by 16 mAbs to the epitopes on the N and C domains of ACE was estimated using an immune-capture enzymatic plate precipitation assay. The precipitation pattern of blood ACE by a set of mAbs was substantially influenced by the presence of ACE inhibitors with the most dramatic local conformational change noted in the N-domain region recognized by mAb 1G12. The ‘‘short’ ’ ACE inhibitor enalaprilat (tripeptide analog) and ‘‘long’’ inhibitor Teprotide (nonapeptide) produced strikingly different mAb 1G12 binding with enalaprilat strongly increasing mAb 1G12 binding and Teprotide decreasing binding. Reduction in S-S bonds via glutathione and dithiothreitol treatment increased 1G12 binding to blood ACE in a manner comparable to enalaprilat. Some patients with uremia due to ESRD exhibited significantly increased mAb 1G12 binding to blood ACE and increased ACE activity towards angiotensin I accompanied by reduced ACE inhibition by inhibitory mAbs and ACE inhibitors

  • Conformational Changes of Blood ACE in Chronic Uremia
    PloS one, 2012
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, Alexandr V. Tarasov, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, Sergei M. Danilov
    Abstract:

    Background: The pattern of binding of monoclonal antibodies (mAbs) to 16 epitopes on human angiotensin I-converting enzyme (ACE) comprise a conformational ACE fingerprint and is a sensitive marker of subtle protein conformational changes. Hypothesis: Toxic substances in the blood of patients with uremia due to End Stage Renal Disease (ESRD) can induce local conformational changes in the ACE protein globule and alter the efficacy of ACE inhibitors. Methodology/Principal Findings: The recognition of ACE by 16 mAbs to the epitopes on the N and C domains of ACE was estimated using an immune-capture enzymatic plate precipitation assay. The precipitation pattern of blood ACE by a set of mAbs was substantially influenced by the presence of ACE inhibitors with the most dramatic local conformational change noted in the N-domain region recognized by mAb 1G12. The ‘‘short’’ ACE inhibitor enalaprilat (tripeptide analog) and ‘‘long’’ inhibitor Teprotide (nonapeptide) produced strikingly different mAb 1G12 binding with enalaprilat strongly increasing mAb 1G12 binding and Teprotide decreasing binding. Reduction in S-S bonds via glutathione and dithiothreitol treatment increased 1G12 binding to blood ACE in a manner comparable to enalaprilat. Some patients with uremia due to ESRD exhibited significantly increased mAb 1G12 binding to blood ACE and increased ACE activity towards angiotensin I accompanied by reduced ACE inhibition by inhibitory mAbs and ACE inhibitors. Conclusions/Significance: The estimation of relative mAb 1G12 binding to blood ACE detects a subpopulation of ESRD patients with conformationally changed ACE, which activity is less suppressible by ACE inhibitors. This parameter may potentially serve as a biomarker for those patients who may need higher concentrations of ACE inhibitors upon antihypertensive therapy.

  • Effect of ACE inhibitors on the local conformation of blood ACE in uremia.
    2012
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, Alexandr V. Tarasov, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, Sergei M. Danilov
    Abstract:

    A. The ratio of ACE activities precipitated from the citrated plasma of uremic patients by mAbs 1G12 and 9B9 (1G12/9B9 ratio) and from pooled plasma from healthy volunteers in the presence of enalaprilat (100 nM) – red bars and without the inhibitor – grey bars. B. The data presented on Fig. 5A were also expressed as a percentage of the effect of enalaprilat on the values of 1G12/9B9 ratio for different patients. The red columns show those mAbs for which enalaprilat effect (increase of mAb binding) exceeded 20%. C. The ratio of ACE activities precipitated from the citrated plasma of uremic patients by mAbs 1G12 and 9B9 (1G12/9B9 ratio) and from pooled plasma from healthy volunteers in the presence of Teprotide (1 µM) – blue bars and without the inhibitor – grey bars. D. The data presented on Fig. 5C were also expressed as a percentage of the effect of Teprotide on the values of 1G12/9B9 ratio for different patients. The yellow columns show those mAbs for which Teprotide effect (decrease of mAb binding) exceeded 20%. All other terms and conditions – as in Figure 1. Data are mean ± SD of 3 independent experiments (each in duplicates). *, p

  • Effect of ACE inhibitors on the activity of plasma ACE in uremia.
    2012
    Co-Authors: Maxim N. Petrov, Valery Y. Shilo, Alexandr V. Tarasov, David E. Schwartz, Joe G. N. Garcia, Olga A. Kost, Sergei M. Danilov
    Abstract:

    A–D Citrated plasma samples of uremic patients with normal (patients #14 and #2) and high (patients #11 and #13) 1G12/9B9 ratio (versus healthy controls, #11 and #19) were incubated with “short” ACE inhibitor enalaprilat (100 nM, A and B) and “long” ACE inhibitor Teprotide (1 µM, C and D) for 1 hour. Data are presented as a residual ACE activity determined with “short” substrate ZPHL (0.5 mM, A and C) and “long” substrate angiotensin I (0.3 mM, B and D). Data are presented as a residual ACE activity. E. The ratio of the rates of the hydrolysis of angiotensin I and ZPHL (angiotensin I/ZPHL ratio) for corresponding samples. F. mAb1G12/9B9 binding ratio for corresponding samples expressed as % from the mean value for healthy persons. Grey bars – inhibition of ACE activity (A–D) or parameters measured in E–F in uremic samples was not differed from that for healthy patients with low 1G12/9B9 ratio. Red bars –measured parameters were statistically higher than that in healthy patients with low (normal) 1G12/9B9 ratio *, p