Innate immune response in the pathogenesis of heart failure in survivors of myocardial infarction

Abstract

Among the different cardiovascular disease complications, atherosclerosis-induced myocardial infarction (MI) is the major contributor of heart failure (HF) and loss of life. This review presents short- and long-term features of post-MI in human hearts and animal models. It is known that the heart does not regenerate, and thus loss of cardiac cells after an MI event is permanent. In survivors of a heart attack, multiple neurohumoral adjustments as well as simultaneous remodeling in both infarcted and noninfarcted regions of the heart help sustain pump function post-MI. In the early phase, migration of inflammatory cells to the infarcted area helps repair and remove the cell debris, while apoptosis results in the elimination of damaged cardiomyocytes, and there is an increase in the antioxidant response to protect the survived myocardium against oxidative stress (OS) injury. However, in the late phase, it appears that there is a relative increase in OS and activation of the innate inflammatory response in cardiomyocytes without any obvious inflammatory cells. In this late stage in survivors of MI, a progressive slow activation of these processes leads to apoptosis, fibrosis, cardiac dysfunction, and HF. Thus, this second phase of an increase in OS, innate inflammatory response, and apoptosis results in wall thinning, dilatation, and consequently HF. It is important to note that this inflammatory response appears to be innate to cardiomyocytes. Blunting of this innate immune cardiomyocyte response may offer new hope for the management of HF.

Weighted Gene Co-Expression Network Analysis Identifies Critical Genes in the Development of Heart Failure After Acute Myocardial Infarction

“…The gene changes within the blue module were strongly induced on the first day of AMI, upon admission to the health care facility. These results suggested that the extent of myocardial damage during the acute phase is closely associated with the stable heart function progressing into HF (Epelman et al, 2015; Zimmer et al, 2019). The identified transcripts present during the first day of AMI can serve as a tool contributing to early diagnosis of the development of HF after AMI.…”

“…Their results provided deep insights into the critical roles of lncRNAs in the pathology of HF. However, the genes identified by Pang et al came from patients with HF including ischemic and non-ischemic causes, which have been shown to be heterogeneous in terms of clinical presentation and prognosis (Zimmer et al, 2019). Our study identified the key genes in HF post-AMI, and determined the role the key genes as early prognostic biomarkers.…”

“…Peripheral blood cells are therefore an attractive alternative to cardiac biopsies. Numerous studies have demonstrated that PBMCs play important roles in the systemic and local inflammation associated with pathological remodeling after AMI (Epelman et al, 2015; Zimmer et al, 2019). Moreover, gene expression profiles of PBMCs and cardiomyocytes share common features in response to aldosterone treatment in hypertensive rats (Gerling et al, 2013), suggesting that transcriptional signatures of PBMCs may serve as early sentinels predictive of pathological remodeling.…”

Combination of Amlexanox and Forskolin Attenuates Pathological Cardiac Hypertrophy by Subduing Maladaptive Inflammatory Response

“…2a). Although we are not the first to demonstrate the hyperactive inflammatory responses of immune cells to either cDAMP or LPS during CCS (Laukova M et al, 2018;Zimmer A et al, 2019), we are to first to profile and compare the two to show the similarity in their proinflammatory and anti-inflammatory cytokine expressions (Fig. 2b).…”

Cardiac tissue engineering: state-of-the-art methods and outlook

“…The adult mammalian heart is among the least regenerative organs thus cardiomyocytes (CMs) are threatened by a multitude of factors; such as necrosis, apoptosis, and oncosis (or ischemic cell death), which may lead to heart failure [1, 2]. Necrosis, or premature cell death due to physical or chemical injury, and apoptosis, or programmed cell death, have more recently been found to be linked together during pathological states of heart disease [3]. Regarding cardiac pathogenesis, myocardial infarction results in scar tissue, regions where CMs are replaced with fibrillar collagen and/or fibroblast-like cells [4].…”