Roles and Mechanisms of Interleukin-12 Family Members in Cardiovascular Diseases: Opportunities and Challenges

Abstract

Cardiovascular diseases represent a complex group of clinical syndromes caused by a variety of interacting pathological factors. They include the most extensive disease population and rank first in all-cause mortality worldwide. Accumulating evidence demonstrates that cytokines play critical roles in the presence and development of cardiovascular diseases. Interleukin-12 family members, including IL-12, IL-23, IL-27 and IL-35, are a class of cytokines that regulate a variety of biological effects; they are closely related to the progression of various cardiovascular diseases, including atherosclerosis, hypertension, aortic dissection, cardiac hypertrophy, myocardial infarction, and acute cardiac injury. This paper mainly discusses the role of IL-12 family members in cardiovascular diseases, and the molecular and cellular mechanisms potentially involved in their action in order to identify possible intervention targets for the prevention and clinical treatment of cardiovascular diseases.

Updating concepts on atherosclerotic inflammation: From pathophysiology to treatment

“…In particular, the TNF‐related apoptosis‐inducing ligand (TRAIL) and the TNF‐like weak inducer of apoptosis (TWEAK) are involved in several processes related to plaque growth and instability, such as endothelial damage, basal membrane remodelling and vascular smooth muscle proliferation 117,118 . Among novel potential therapeutic target, the IL‐12 superfamily members, particularly IL‐35, have been associated with myocardial reperfusion damage in murine models 119 . Since the monoclonal inhibitor of IL‐12 ustekinumab is currently approved for the treatment of chronic inflammatory bowel diseases, 120 there is a potential rationale for clinical trials.…”

Significant association between rs28362491 polymorphism in NF-κB1 gene and coronary artery disease: a meta-analysis

“…The in vitro study revealed that the D allele in rs28362491 polymorphism might result in reduced NF-κB1 message, thus decreasing the expression of NF-κB1 [39]. The NF-κB1 appears to be specifically involved in anti-inflammatory effects, and decreased NF-κB1 can promote the transcription of pro-inflammatory cytokines like TNF-α and IL-12 [40], which are contributors of CAD [41,42].…”

Antibody-Based Therapeutics for Atherosclerosis and Cardiovascular Diseases

“…Conversely, when the function of IL-12 was neutralized using vaccination in LDL receptor-knockout mice, atherogenesis was reduced by 68.5% [ 130 , 131 ]. The levels of IL-12 family cytokines are also significantly higher in patients with atherosclerosis associated with cardiovascular disease [ 132 , 133 ].…”