Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin

Sotirios N Sotiriou, Valeria V Orlova, Nadia Al-Fakhri, Eveliina Ihanus, Matina Economopoulou, Berend Isermann, Khalil Bdeir, Peter P Nawroth, Klaus T Preissner, Carl G Gahmberg, Marlys L Koschinsky, Triantafyllos Chavakis

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    Sammanfattning

    Lipoprotein(a) [Lp(a)], consisting of LDL and the unique constituent apolipoprotein(a) [apo(a)], which contains multiple repeats resembling plasminogen kringle 4, is considered a risk factor for the development of atherosclerotic disorders. However, the underlying mechanisms for the atherogenicity of Lp(a) are not completely understood. Here, we define a novel function of Lp(a) in promoting inflammatory cell recruitment that may contribute to its atherogenicity. Through its apo(a) moiety Lp(a) specifically interacts with the beta 2-integrin Mac-1, thereby promoting the adhesion of monocytes and their transendothelial migration in a Mac-1-dependent manner. Interestingly, the interaction between Mac-1 and Lp(a) was strengthened in the presence of proatherogenic homocysteine and was blocked by plasminogen/angiostatin kringle 4. Through its interaction with Mac-1, Lp(a) induced activation of the proinflammatory transcription factor NF kappa B, as well as the NF kappa B-related expression of prothrombotic tissue factor. In atherosclerotic coronary arteries Lp(a) was found to be localized in close proximity to Mac-1 on infiltrating mononuclear cells. Taken together, our data demonstrate that Lp(a), via its apo(a) moiety, is a ligand for the beta 2-integrin Mac-1, thereby facilitating inflammatory cell recruitment to atherosclerotic plaques. These observations suggest a novel mechanism for the atherogenic properties of Lp(a).
    Originalspråkengelska
    TidskriftFASEB Journal
    Volym20
    Sidor (från-till)559-561
    Antal sidor3
    ISSN0892-6638
    DOI
    StatusPublicerad - 2006
    MoE-publikationstypA1 Tidskriftsartikel-refererad

    Citera det här

    Sotiriou, S. N., Orlova, V. V., Al-Fakhri, N., Ihanus, E., Economopoulou, M., Isermann, B., ... Chavakis, T. (2006). Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin. FASEB Journal, 20, 559-561. https://doi.org/10.1096/fj.05-4857fje
    Sotiriou, Sotirios N ; Orlova, Valeria V ; Al-Fakhri, Nadia ; Ihanus, Eveliina ; Economopoulou, Matina ; Isermann, Berend ; Bdeir, Khalil ; Nawroth, Peter P ; Preissner, Klaus T ; Gahmberg, Carl G ; Koschinsky, Marlys L ; Chavakis, Triantafyllos. / Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin. I: FASEB Journal. 2006 ; Vol. 20. s. 559-561.
    @article{55eea30b926c478d824e0aea3bc666bf,
    title = "Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin",
    abstract = "Lipoprotein(a) [Lp(a)], consisting of LDL and the unique constituent apolipoprotein(a) [apo(a)], which contains multiple repeats resembling plasminogen kringle 4, is considered a risk factor for the development of atherosclerotic disorders. However, the underlying mechanisms for the atherogenicity of Lp(a) are not completely understood. Here, we define a novel function of Lp(a) in promoting inflammatory cell recruitment that may contribute to its atherogenicity. Through its apo(a) moiety Lp(a) specifically interacts with the beta 2-integrin Mac-1, thereby promoting the adhesion of monocytes and their transendothelial migration in a Mac-1-dependent manner. Interestingly, the interaction between Mac-1 and Lp(a) was strengthened in the presence of proatherogenic homocysteine and was blocked by plasminogen/angiostatin kringle 4. Through its interaction with Mac-1, Lp(a) induced activation of the proinflammatory transcription factor NF kappa B, as well as the NF kappa B-related expression of prothrombotic tissue factor. In atherosclerotic coronary arteries Lp(a) was found to be localized in close proximity to Mac-1 on infiltrating mononuclear cells. Taken together, our data demonstrate that Lp(a), via its apo(a) moiety, is a ligand for the beta 2-integrin Mac-1, thereby facilitating inflammatory cell recruitment to atherosclerotic plaques. These observations suggest a novel mechanism for the atherogenic properties of Lp(a).",
    author = "Sotiriou, {Sotirios N} and Orlova, {Valeria V} and Nadia Al-Fakhri and Eveliina Ihanus and Matina Economopoulou and Berend Isermann and Khalil Bdeir and Nawroth, {Peter P} and Preissner, {Klaus T} and Gahmberg, {Carl G} and Koschinsky, {Marlys L} and Triantafyllos Chavakis",
    year = "2006",
    doi = "10.1096/fj.05-4857fje",
    language = "English",
    volume = "20",
    pages = "559--561",
    journal = "FASEB Journal",
    issn = "0892-6638",
    publisher = "Federation of American Societies for Experimental Biology",

    }

    Sotiriou, SN, Orlova, VV, Al-Fakhri, N, Ihanus, E, Economopoulou, M, Isermann, B, Bdeir, K, Nawroth, PP, Preissner, KT, Gahmberg, CG, Koschinsky, ML & Chavakis, T 2006, 'Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin', FASEB Journal, vol. 20, s. 559-561. https://doi.org/10.1096/fj.05-4857fje

    Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin. / Sotiriou, Sotirios N; Orlova, Valeria V; Al-Fakhri, Nadia; Ihanus, Eveliina; Economopoulou, Matina; Isermann, Berend; Bdeir, Khalil; Nawroth, Peter P; Preissner, Klaus T; Gahmberg, Carl G; Koschinsky, Marlys L; Chavakis, Triantafyllos.

    I: FASEB Journal, Vol. 20, 2006, s. 559-561.

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    TY - JOUR

    T1 - Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin

    AU - Sotiriou, Sotirios N

    AU - Orlova, Valeria V

    AU - Al-Fakhri, Nadia

    AU - Ihanus, Eveliina

    AU - Economopoulou, Matina

    AU - Isermann, Berend

    AU - Bdeir, Khalil

    AU - Nawroth, Peter P

    AU - Preissner, Klaus T

    AU - Gahmberg, Carl G

    AU - Koschinsky, Marlys L

    AU - Chavakis, Triantafyllos

    PY - 2006

    Y1 - 2006

    N2 - Lipoprotein(a) [Lp(a)], consisting of LDL and the unique constituent apolipoprotein(a) [apo(a)], which contains multiple repeats resembling plasminogen kringle 4, is considered a risk factor for the development of atherosclerotic disorders. However, the underlying mechanisms for the atherogenicity of Lp(a) are not completely understood. Here, we define a novel function of Lp(a) in promoting inflammatory cell recruitment that may contribute to its atherogenicity. Through its apo(a) moiety Lp(a) specifically interacts with the beta 2-integrin Mac-1, thereby promoting the adhesion of monocytes and their transendothelial migration in a Mac-1-dependent manner. Interestingly, the interaction between Mac-1 and Lp(a) was strengthened in the presence of proatherogenic homocysteine and was blocked by plasminogen/angiostatin kringle 4. Through its interaction with Mac-1, Lp(a) induced activation of the proinflammatory transcription factor NF kappa B, as well as the NF kappa B-related expression of prothrombotic tissue factor. In atherosclerotic coronary arteries Lp(a) was found to be localized in close proximity to Mac-1 on infiltrating mononuclear cells. Taken together, our data demonstrate that Lp(a), via its apo(a) moiety, is a ligand for the beta 2-integrin Mac-1, thereby facilitating inflammatory cell recruitment to atherosclerotic plaques. These observations suggest a novel mechanism for the atherogenic properties of Lp(a).

    AB - Lipoprotein(a) [Lp(a)], consisting of LDL and the unique constituent apolipoprotein(a) [apo(a)], which contains multiple repeats resembling plasminogen kringle 4, is considered a risk factor for the development of atherosclerotic disorders. However, the underlying mechanisms for the atherogenicity of Lp(a) are not completely understood. Here, we define a novel function of Lp(a) in promoting inflammatory cell recruitment that may contribute to its atherogenicity. Through its apo(a) moiety Lp(a) specifically interacts with the beta 2-integrin Mac-1, thereby promoting the adhesion of monocytes and their transendothelial migration in a Mac-1-dependent manner. Interestingly, the interaction between Mac-1 and Lp(a) was strengthened in the presence of proatherogenic homocysteine and was blocked by plasminogen/angiostatin kringle 4. Through its interaction with Mac-1, Lp(a) induced activation of the proinflammatory transcription factor NF kappa B, as well as the NF kappa B-related expression of prothrombotic tissue factor. In atherosclerotic coronary arteries Lp(a) was found to be localized in close proximity to Mac-1 on infiltrating mononuclear cells. Taken together, our data demonstrate that Lp(a), via its apo(a) moiety, is a ligand for the beta 2-integrin Mac-1, thereby facilitating inflammatory cell recruitment to atherosclerotic plaques. These observations suggest a novel mechanism for the atherogenic properties of Lp(a).

    U2 - 10.1096/fj.05-4857fje

    DO - 10.1096/fj.05-4857fje

    M3 - Article

    VL - 20

    SP - 559

    EP - 561

    JO - FASEB Journal

    JF - FASEB Journal

    SN - 0892-6638

    ER -