Therapeutics: Atherosclerosis and Cardiovascular Diseases
Cardiovascular disease is the leading cause of death worldwide, and its prevalence is increasing due to the aging of societies. Atherosclerosis, a type of chronic inflammatory disease that occurs in arteries, is considered to be the main cause of cardiovascular diseases such as ischemic heart disease or stroke. In addition, the inflammatory response caused by atherosclerosis confers a significant effect on chronic inflammatory diseases such as psoriasis and rheumatic arthritis.
Cardiovascular disease is the leading cause of death worldwide, and its prevalence is increasing due to the aging of societies. Atherosclerosis, a type of chronic inflammatory disease that occurs in arteries, is considered to be the main cause of cardiovascular diseases such as ischemic heart disease or stroke. In addition, the inflammatory response caused by atherosclerosis confers a significant effect on chronic inflammatory diseases such as psoriasis and rheumatic arthritis. Here, we review the mechanism of action of the main causes of atherosclerosis such as plasma LDL level and inflammation; furthermore, we review the recent findings on the preclinical and clinical effects of antibodies that reduce the LDL level and those that neutralize the cytokines involved in inflammation. The apolipoprotein B autoantibody and anti-PCSK9 antibody reduced the level of LDL and plaques in animal studies, but failed to significantly reduce carotid inflammation plaques in clinical trials. The monoclonal antibodies against PCSK9 (alirocumab, evolocumab), which are used as a treatment for hyperlipidemia, lowered cholesterol levels and the incidence of cardiovascular diseases. Antibodies that neutralize inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17, and IL-12/23) have shown promising but contradictory results and thus warrant further research.
2. Cardiovascular disease
|Therapeutic/Study Name||Antibody Name||Target||Patients||Result|
|GLACIER||MLDL1278A||oxLDL (MDA-modified human ApoB-100)||CVD patients||Non significantly reduce carotid plaque|
|FOURIER||Evolocumab||PCSK9||patients with clinically evident CVD(prior MI, stroke or PAD)||LDL-C level and primary outcomes (MI, stroke, cardiovascular death, coronary revascularization, unstable angina) reduction|
|ODYSSEY||Alirocumab||PCSK9||patients diagnosed with ACS||LDL-C level and primary outcomes (non-fatal MI, ischemic stroke, unstable angina) reduction|
|SPIRE||Bococizumab||PCSK9||CV or high risk patients||LDL-C level and primary ennpoint reduction in LDL-C >100 mg/dL group|
|ATTACH||Infliximab||TNF-α||Heart failure||Deteriorated heart failure|
|STROBE (follow up study)||Infliximab||TNF-α||Psoriasis||Significantly reduce the cardiovascular risk|
|Di Minno et al. ||Adalimumab, Infliximab||TNF-A||Psoriatic arthritis||Decreased atherosclerosis of carotid artery|
|CANTOS||Canakinumab||IL-1B||CAD after MI + hsCRP||Decreased hsCRP level and incidence of the primary endpoint (nonfatal myocardial infarction, stroke, cardiovascular death)|
|ASSIL-MI||Tocilizumab||IL-6||ACS||Increased myocardial salvage|
|Mease et al. ||Secukinumab||IL-17||Psoriatic arthritis||Non significant increased MACE|
|Uncover||Ixekizumab||IL-17||Moderate to severe psoriasis||Reduced Psoriasis Area and Severity Index (PASI) score|
|Langley et al. ||Briakinumab||IL-12/23||Psoriasis||Increased MACE|
|Uniti||Ustekinumab||IL-12/23||Moderate to severe Crohn’s disease||Significantly higher rate of response|
The entry is from 10.3390/ijms22115770
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