DHA Supplementation Attenuates MI-Induced LV Matrix Remodeling and Dysfunction in Mice

Abstract

Objective. Myocardial ischemia and reperfusion (I/R) injury is associated with oxidative stress and inflammation, leading to scar development and malfunction. The marine omega-3 fatty acids (ω-3 FA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are mediating cardioprotection and improving clinical outcomes in patients with heart disease. Therefore, we tested the hypothesis that docosahexaenoic acid (DHA) supplementation prior to LAD occlusion-induced myocardial injury (MI) confers cardioprotection in mice. Methods. C57BL/6N mice were placed on DHA or control diets (CD) beginning 7 d prior to 60 min LAD occlusion-induced MI or sham surgery. The expression of inflammatory mediators was measured via RT-qPCR. Besides FACS analysis for macrophage quantification and subtype evaluation, macrophage accumulation as well as collagen deposition was quantified in histological sections. Cardiac function was assessed using a pressure-volume catheter for up to 14 d. Results. DHA supplementation significantly attenuated the induction of peroxisome proliferator-activated receptor-α (PPAR-α) (2.3±0.4 CD vs. 1.4±0.3 DHA) after LAD occlusion. Furthermore, TNF-α (4.0±0.6 CD vs. 1.5±0.2 DHA), IL-1β (60.7±7.0 CD vs. 11.6±1.9 DHA), and IL-10 (223.8±62.1 CD vs. 135.5±38.5 DHA) mRNA expression increase was diminished in DHA-supplemented mice after 72 h reperfusion. These changes were accompanied by a less prominent switch in α/β myosin heavy chain isoforms. Chemokine mRNA expression was stronger initiated (CCL2 6 h: 32.8±11.5 CD vs. 78.8±13.6 DHA) but terminated earlier (CCL2 72 h: 39.5±7.8 CD vs. 8.2±1.9 DHA; CCL3 72 h: 794.3±270.9 CD vs. 258.2±57.8 DHA) in DHA supplementation compared to CD mice after LAD occlusion. Correspondingly, DHA supplementation was associated with a stronger increase of predominantly alternatively activated Ly6C-positive macrophage phenotype, being associated with less collagen deposition and better LV function (EF 14 d: 17.6±2.6 CD vs. 31.4±1.5 DHA). Conclusion. Our data indicate that DHA supplementation mediates cardioprotection from MI via modulation of the inflammatory response with timely and attenuated remodeling. DHA seems to attenuate MI-induced cardiomyocyte injury partly by transient PPAR-α downregulation, diminishing the need for antioxidant mechanisms including mitochondrial function, or α- to β-MHC isoform switch.

Immunoregulatory Effect of Preventive Supplementation of Omega-3 Fatty Acid in a Complex Regional Pain Syndrome Type I Model in Mice

“…It may, therefore, be useful to consider related literature as a context for our findings regarding omega-3 effects on IL-10. The most relevant finding is that C57BL/6N mice receiving a diet rich in DHA (Linoleic 2.9 g/kg, Linolenic 0.43 g/kg, and DHA 0.26 g/kg) for 7 days before myocardial I/R displayed decreased IL-10 mRNA expression 72 h after reperfusion, similar to our findings at 2 days post-CPIP ( Habicht et al, 2020 ). Furthermore, DHA supplementation also reduced TNF and IL-1β expression at 72 h post-I/R injury and was associated with a strong increase in the phenotype of alternatively activated Ly6C + macrophages at 14 days post-injury ( Habicht et al, 2020 ).…”

The histone demthylase KDM3A protects the myocardium from ischemia/reperfusion injury via promotion of ETS1 expression

“…ROS generation and inflammation also act as preferential agents in response to myocardial I/R insult despite apoptotic cascades 5 , 33 . To further reveal KDM3A’s participation in modulating ROS formation, in situ DHE staining together with the activity of antioxidative SOD and the content of the oxidative marker MDA were determined essentially.…”

“…Once oxidative stress disrupts the balance between antioxidant defence and ROS in favour of the latter, it constitutes a crucial aetiological component of MIRI 10 . Excessive ROS elicits an imbalanced redox status, particularly as reflected by the inactivation of the antioxidant enzyme SOD and increased MDA levels 11 , 14 , 33 . Furthermore, inflammation has been proposed to aggravate MIRI 5 .…”

“…To induce myocardial overexpression of KDM3A in vivo, male SD rats (SPF grade, weighing 220–250 g) were purchased from Vital River Laboratories (VRL, Beijing, China). Cardiac-specific KDM3A overexpression in vivo was garnered by intramyocardial injection of AdKDM3A 32 , 33 . Male SD rats (SPF grade, weighing 220–250 g) were purchased from Vital River Laboratories (VRL, Beijing, China).…”

β-caryophyllene and docosahexaenoic acid, isolated or associated, have potential antinociceptive and anti-inflammatory effects in vitro and in vivo

“…IL-10 acts primarily with immunosuppressive functions on leukocytes, whereas other members of the family act preferentially on epithelial cells, where they control defense mechanisms against viral, bacterial, and fungal infections, protect tissue integrity, and promote repair and regeneration 32,33 . DHA supplementation promotes the reduction of IL-10 synthesis by conferring cardioprotection in a myocardial injury model 34 . A study with the essential oil of Polygonum minus identified BCP as one of its components and used it as a positive control in the cisplatin-induced hepatotoxicity model, demonstrating a reduction in the concentration of IL-10 and, therefore, hepatoprotection 35 www.nature.com/scientificreports/ the reduction in our study demonstrates protection against exacerbation of inflammation during the infectious process.…”