Inhibition of Neointima Formation through DNA Vaccination for Apolipoprotein(a): A New Therapeutic Strategy for Lipoprotein(a)

Kyutoku, Mariko; Nakagami, Hironori; Kuroda, Hiroshi; Nakagami, Futoshi; Shimamura, Munehisa; Kurinami, Hitomi; Tomioka, H.; Miyake, Takashi; Katsuya, Tomohiro; Morishita, Ryuichi

doi:10.1038/srep01600

Cited by 5 publications

(3 citation statements)

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“…31) Lp(a) is a unique plasma lipoprotein that consists of a cholesterol-rich LDL particle with one molecule each of apolipoprotein B-100 (apoB) and apolipoprotein (a) [apo(a)], which are bound through a single disulfide bond. 32) Lp(a) is found only in humans, primates and hedgehogs.…”

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confidence: 99%

“…Thus, to inhibit the biological activity of Lp(a), we developed a DNA vaccine for apo(a) that targets 12 selected hydrophilic amino acids in the kringle-4 type 2 domain of apo(a) (Figure 2). 31) Hepatitis B virus core protein was used as an epitope carrier to enhance the immunogenicity. Intramuscular immunization with apo(a) vaccine resulted in signifi cant inhibition of neointima formation in a carotid artery ligation model using Lp(a) transgenic mice, 1-10), a kringle Vlike domain, and repeated kringle IV type2 (IV type2) variable repeats.…”

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Therapeutic Vaccines for Hypertension and Dyslipidemia

2014

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SummaryVaccines are commonly used as a preventive medicine for infectious diseases worldwide, however, clinical trials on an amyloid beta vaccine for Alzheimer's disease represents a new concept in the fi eld of vaccinations. Several recent studies indicate the potential of therapeutic vaccines as well as classical vaccines as preventive medicines. A number of therapeutic vaccines for cancer have been developed as novel immunotherapies. Their targets are usually specifi c antigens in cancer cells, allowing activated cytotoxic T cells (CTLs) to attach and remove the antigen-presenting cancer cells. Recently, we and others have attempted to develop a therapeutic vaccine against hypertension. The vaccine target is angiotensin II (AngII), and induced anti-AngII antibodies could effi ciently ameliorate high blood pressure. However, because AngII is an endogenous hormone, we must avoid the induction of autoimmune diseases by administration of an AngII vaccine. Therefore, our system was used to design a therapeutic vaccine that elicits anti-AngII antibodies without CTL activation against AngII. Because the target antigen itself does not include T cell epitopes, the immunogenic molecule (ie, KLH) provides antigen that supports the activation of T cells. In particular, helper T cells may activate B cells that produce antibodies against our specifi c antigen. In this review, we will explain our concept of therapeutic vaccines based on our recent data. (Int Heart J 2014; 55: 96-100) Key words: Angiotensin II, Lipoprotein(a) V accines are commonly used worldwide to protect against infectious diseases, and clinical trials for amyloid beta vaccines against Alzheimer's disease, cancer and rheumatoid arthritis will usher in a new era in vaccination.1-6) We will pursue the development of a vaccine for patients with high blood pressure. The number of patients with hypertension increases each year, and several types of antihypertensive drugs are available for treatment. Antihypertensive drugs are effective with few side effects, however, patients often need to take two or three drugs at a time to control severe hypertension. Therefore, the increased medical costs associated with treating hypertension might become a fi scal and social problem that affects social security expenses. The ultimate goal of our study is to reduce medical costs through the clinical use of a therapeutic vaccine for hypertension.However, when considering clinical applications, the safety of therapeutic vaccines should be carefully examined. In the history of therapeutic vaccines, the amyloid beta vaccine effectively reduced amyloid plaques and restored memory function in several animal models of Alzheimer's disease. [3][4][5] Unfortunately, however, the clinical trial for this vaccine was halted because 6% of the participants developed aseptic meningoencephalitis, even though amyloid plaque reduction was observed.4,7) Postmortem examination of the brains of two patients who suffered from aseptic meningoencephalitis due to the vaccine revealed T lymphocyte i...

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Therapeutic Vaccines for Hypertension and Dyslipidemia

2014

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“…Newer antisense nucleotides therapy such as pelacarsen depending on the drug doses used, has led to dramatic Lp(a) levels reductions, namely 72% at the dose of 60 mg per month and 80% at the dose of 20 mg per week, making it possible to achieve the target of Lp(a) <50 mg/dL [13][14][15] .…”

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