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.

Choi YJ, et al. J Cardiovasc Imaging. 2022 Nov;31:e2. https://doi.org/10.4250/jcvi.2022.0076

Aortic stenosis (AS) is a severe heart valve disease marked by calcification, leading to heart failure. This study examined mitochondrial function in human aortic valve interstitial cells isolated from patients with AS and tested spermidine, an autophagy inducer as AS treatment. Spermidine treatment reduced fibrosis and calcification in human aortic valve interstitial cells and improved these features in spermidine-treated mice. The AKT-TP53-DNMT1-PPARG pathway was implicated, and DNA methyltransferase 1 inhibition by 5-azacytidine enhanced mitochondrial biogenesis by reducing mitochondrial DNA hypermethylation. These findings suggest that spermidine or DNA methyltransferase 1 inhibition could prevent aortic valve disease by improving mitochondrial function.

We present data showing that Iodotyrosine Deiodinase (IYD) is a dual-function enzyme acting as a catalyst in metabolism and a receptor for cooperative stem cell differentiation. IYD is present both in thyroid cells where it is critical for scavenging iodine from halogenated by-products of thyroid hormone production and on hematopoietic stem cells. To close the cooperative loop, the mono- and di-Iodotyrosine (MIT and DIT) substrates of IYD in the thyroid are also agonists for IYD now acting as a receptor on bone marrow stem cells. While studying intracellular combinatorial antibody libraries, we discovered an agonist antibody, H3 Ab, of which the target is the enzyme IYD. When agonized by H3 Ab, IYD expressed on stem cells induces differentiation of the cells into brown adipocyte-like cells, which selectively migrate to mouse heart tissue. H3 Ab also binds to IYD expressed on human myocardium. Thus, one has a single enzyme acting in different ways on different cells for the cooperative purpose of enhancing thermogenesis or of regenerating damaged heart tissue.

BACKGROUND: The timing of surgery in asymptomatic severe mitral regurgitation remains controversial. This observational study sought to compare long-term outcomes of early surgery with a conventional treatment strategy in asymptomatic patients with severe mitral regurgitation. METHODS: From 1996 to 2016, a total of 1063 consecutive asymptomatic patients (673 men; mean±SD age, 51±14 years) with severe degenerative mitral regurgitation and preserved left ventricular function were enrolled, and followed prospectively for a median of 12 years (interquartile range, 8–17 years). Early surgery was performed on 545 patients and the conventional treatment strategy was chosen for 518 patients. We compared overall and cardiac mortality rates between these 2 treatment strategies using propensity score adjustment. RESULTS: In the early surgery group, no operative deaths occurred, and mitral valve repair was successfully performed in 97% of patients. During follow-up, 8 (1.5%) patients in the early surgery group and 54 (10.4%) in the conventional management group died from cardiovascular causes (hazard ratio, 0.17 [95% CI, 0.07–0.40]; P <0.001). A total of 74 (13.6%) deaths from any cause occurred in the early surgery group, whereas 116 (22.4%) occurred in the conventional management group (hazard ratio, 0.72 [95% CI, 0.52–0.99]; P =0.046). For the 358 propensity score matched pairs, the early surgery group had a significantly lower risk of cardiac mortality than the conventional treatment group (hazard ratio, 0.18 [95% CI, 0.08–0.43]; P <0.001) and significantly lower cardiac mortality rates (5.6% versus 17.4% at 20 years; P =0.002). Compared with the conventional treatment group, the early surgery group also had a significantly lower risk of overall mortality (hazard ratio, 0.66 [95% CI, 0.47–0.93]; P =0.018) and significantly lower overall mortality rates (28.2% versus 33.9% at 20 years; P =0.015). CONCLUSIONS: Compared with conventional management, early surgery is associated with better long-term outcomes among asymptomatic patients with severe mitral regurgitation and preserved left ventricular function. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01703806.