Pyrroloquinoline quinone attenuates isoproterenol hydrochloride‑induced cardiac hypertrophy in AC16 cells by inhibiting the NF‑κB signaling pathway

Abstract

Pyrroloquinoline quinone (PQQ) is a naturally occurring redox co-factor that functions as an essential nutrient and antioxidant, and has been reported to exert potent anti-inflammatory effects. However, the therapeutic potential of PQQ for isoproterenol hydrochloride (Iso)-induced cardiac hypertrophy has not yet been explored, at least to the best of our knowledge. In the present study, the anti-inflammatory effects of PQQ were investigated in Iso-treated AC16 cells, a myocardial injury cellular model characterized by an increase in the apparent surface area of the cells and the activation of intracellular cardiac hypertrophy-associated proteins. The results revealed that pre-treatment with PQQ significantly inhibited the expression of cardiac hypertrophy marker proteins, such as atrial natriuretic peptide, brain natriuretic peptide and β-myosin heavy chain. PQQ also inhibited the activation of the nuclear factor (NF)-κB signaling pathway in Iso-treated AC16 cells, thus inhibiting the nuclear translocation of NF-κB and reducing the phosphorylation levels of p65. On the whole, the findings of this study suggest that PQQ may be a promising therapeutic agent for effectively reversing the progression of cardiac hypertrophy.

Pyrroloquinoline quinone ameliorates diabetic cardiomyopathy by inhibiting the pyroptosis signaling pathway in C57BL/6 mice and AC16 cells

“…Previous studies have reported effects of PQQ on AC16 cells at different concentrations and on other cell types. Wen et al found that PQQ had no effect on AC16 cells at concentrations from 1 to 200 μmol/L [ 10 ]. In our study, although PQQ had no statistically significant effect on cell viability at concentrations from 1 to 10,000 nmol/L, it had adverse effects on AC16 cells at 100,000 nmol/L.…”

“…Pyrroloquinoline quinone (PQQ), a natural bioactive substance, is a water-soluble redox coenzyme that is considered to be a new B vitamin [ 6 ]. PQQ is distributed widely in multiple dietary sources and exhibits potential health benefits, such as anti-inflammatory [ 7 ], anti-oxidative [ 8 ], anti-diabetic [ 9 ], and cardioprotective effects [ 10 ]. Several studies have demonstrated that PQQ deficiency leads to immune dysfunction, growth impairment, and abnormal reproductive performance [ 11 ].…”

“…Pyroptosis, which is characterized by the activation of the Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, is a type of programmed cell death associated with inflammation [ 10 ]. Recent studies have demonstrated that pyroptosis is associated with DCM [ 16 ] .…”

Human Cell Modeling for Cardiovascular Diseases

“…Emerging technologies will allow in the future an increasingly precise understanding of the pathophysiology of CVDs and consequent therapeutic advancements. Arrhythmogenic Cardiomyopathy Pathogenic mechanism [8] BMCs Arrhythmogenic Cardiomyopathy Pathogenic mechanism [10] Heart failure - [11] CMs Heart failure Pathogenic mechanism [14] Hypertrophic Cardiomyopathy Drug discovery [16,17] C-MSCs Myocardial ischemia Pathogenic mechanism [24] Arrhythmogenic Cardiomyopathy Pathogenic mechanism/Involvement in disease pathogenesis [25] c-kit + C-MSCs Atrial Fibrillation Pathogenic mechanism [31] FAPs Arrhythmogenic Cardiomyopathy Involvement in disease pathogenesis [35] ECs Hypertension Pathogenic mechanism [39,43] Atherosclerosis Pathogenic mechanism/Involvement in disease pathogenesis [41] Pathogenic mechanism [42] VSMCs Hypertension Involvement in disease pathogenesis [48] Pathogenic mechanism [49] Atherosclerosis Differentiation phenotypes [46] Pathogenic mechanism/Drug discovery [47] AC 16 Hypertrophic Cardiomyopathy Drug discovery [51] Myocardial ischemia Pathogenic mechanism [52] hESC-CMs Hypertrophic Cardiomyopathy Pathogenic mechanism [64,65] hiPSC-CMs Atrial Fibrillation Pathogenic mechanism [76] Hypertrophic Cardiomyopathy Drug discovery [78] Long QT Syndrome Pathogenic mechanism/Drug discovery [79] hiPSC-ECs Hypertension Drug discovery [81] Moyamoya disease Pathogenic mechanism [82] hiPSC-SMCs Supravalvular aortic stenosis syndrome Pathogenic mechanism [83] Bicuspid Aortic Valve-related Thoracic Aortic Aneurysm Pathogenic mechanism/Drug discovery [84] VSMCs and CD14 + cells co-culture Atherosclerosis Pathogenic mechanism [88] [89] ECs and VSMCs co-culture Atherosclerosis Pathogenic mechanism [90]...…”

“…Recently, AC 16 cells treated with isoproterenol hydrochloride (Iso) were used as a cardiac hypertrophy model: Iso induced an increase in the size of the cells and the activation of cardiac hypertrophy markers, such as atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC). The aim of the work was to test the anti-inflammatory effects of pyrroloquinoline quinone (PQQ), which resulted to attenuate the activation of nuclear factor k-light-chain-enhancer of activated B cells (NF-κB) phosphorylation, to reduce the Iso-induced accumulation of reactive oxygen species (ROS), to inhibit the expression of hypertrophy markers and to increase the level of matrix metalloproteinase (MMP) in cardiac hypertrophic AC 16 cells [ 51 ]. Another work proposed AC 16 CMs as an ischemia/reperfusion (IR) injury model to evaluate the cytoprotective role of yes-associated protein 1 (YAP1), the main effector of Hippo-signaling pathway.…”