Reverse Remodeling in Human Heart Failure after Cardiac Resynchronization Therapy Is Associated With Reduced RHO-Kinase Activation

Ocaranza, María Paz; Jalil, Jorge; Altamirano, Rodrigo; León, Ana de; Moya, Jackeline; Lonis, Alejandra; Gabrielli, Luigi; Nab, Paul Mac; Córdova, Samuel; Paredes, Alejandro; Vergara, Ismael A.; Bittner, Alex; Sabat, Karime; Pastorini, Karla

doi:10.3389/fphar.2021.565724

Cited by 3 publications

(1 citation statement)

References 46 publications

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“…Higher levels of ROCK activity have also been reported in patients with metabolic syndrome (MS) [161,162]. In HFrEF patients, a significant reduction in left atrial diameter was observed three months after effective resynchronization therapy, which was associated with a significant reduction of ROCK activation in circulating leukocytes [163]. Although GLP-1 RA treatment reduced ROCK activation and hypertrophy in cultured cardiac myoblasts stimulated by angiotensin II [155], there are no available human data on the effect of GLP-1 RA on ROCK activation in patients with MS or T2D, and GLP-1 RA may reduce ROCK activation in PBMCs, as well as body weight, plasma glucose, and insulin levels; increase aerobic capacity; and possibly decrease left atrial volume while improving left atrial function, potentially preventing HF in patients with MS or T2D.…”

Section: Effects Of Glp-1r Agonism On the Ras Cardiac Remodeling Path...mentioning

confidence: 95%

New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review

Jalil,

Gabrielli,

Ocaranza

et al. 2024

IJMS

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This review examines the impact of obesity on the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and focuses on novel mechanisms for HFpEF prevention using a glucagon-like peptide-1 receptor agonism (GLP-1 RA). Obesity can lead to HFpEF through various mechanisms, including low-grade systemic inflammation, adipocyte dysfunction, accumulation of visceral adipose tissue, and increased pericardial/epicardial adipose tissue (contributing to an increase in myocardial fat content and interstitial fibrosis). Glucagon-like peptide 1 (GLP-1) is an incretin hormone that is released from the enteroendocrine L-cells in the gut. GLP-1 reduces blood glucose levels by stimulating insulin synthesis, suppressing islet α-cell function, and promoting the proliferation and differentiation of β-cells. GLP-1 regulates gastric emptying and appetite, and GLP-1 RA is currently indicated for treating type 2 diabetes (T2D), obesity, and metabolic syndrome (MS). Recent evidence indicates that GLP-1 RA may play a significant role in preventing HFpEF in patients with obesity, MS, or obese T2D. This effect may be due to activating cardioprotective mechanisms (the endogenous counter-regulatory renin angiotensin system and the AMPK/mTOR pathway) and by inhibiting deleterious remodeling mechanisms (the PKA/RhoA/ROCK pathway, aldosterone levels, and microinflammation). However, there is still a need for further research to validate the impact of these mechanisms on humans.

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Section: Effects Of Glp-1r Agonism On the Ras Cardiac Remodeling Path...mentioning

confidence: 95%

New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review

Jalil,

Gabrielli,

Ocaranza

et al. 2024

IJMS

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Regression of cardiac hypertrophy in health and disease: mechanisms and therapeutic potential

2023

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Role of monocytes and dendritic cells in cardiac reverse remodelling after cardiac resynchronization therapy

Martins,

António,

Rodrigues

et al. 2023

BMC Cardiovasc Disord

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Background and aims Monocytes and dendritic cells (DC) are both key inflammatory cells, with recognized effects on cardiac repair. However, there are distinct subsets of monocytes with potential for beneficial or detrimental effects on heart failure (HF) pathogenesis. The connection between reverse cardiac remodelling, the potential anti-inflammatory effect of cardiac resynchronization therapy (CRT) and monocytes and DC homeostasis in HF is far from being understood. We hypothesized that monocytes and DC play an important role in cardiac reverse remodelling and CRT response. Therefore, we aimed to assess the potential role of baseline peripheral levels of blood monocytes and DC subsets and their phenotypic and functional activity for CRT response, in HF patients. As a secondary objective, we aimed to evaluate the impact of CRT on peripheral blood monocytes and DC subsets, by comparing baseline and post CRT circulating levels and phenotypic and functional activity. Methods Forty-one patients with advanced HF scheduled for CRT were included in this study. The quantification and phenotypic determination of classical (cMo), intermediate (iMo) and non-classical monocytes (ncMo), as well as of myeloid (mDC) and plasmacytoid DC (pDC) were performed by flow cytometry in a FACSCanto™II (BD) flow cytometer. The functional characterization of total monocytes and mDC was performed by flow cytometry in a FACSCalibur flow cytometer, after in vitro stimulation with lipopolysaccharide from Escherichia coli plus interferon (IFN)-γ, in the presence of Brefeldina A. Comparisons between the control and the patient group, and between responders and non-responders to CRT were performed. Results Compared to the control group, HF population presented a significantly lower frequency of pDC at baseline and a higher proportion of monocytes and mDC producing IL-6 and IL-1β, both before and 6-months after CRT (T6). There was a remarkable decrease of cMo and an increase of iMo after CRT, only in responders. The responder group also presented higher ncMo values at T6 compared to the non-responder group. Both responders and non-responders presented a decrease in the expression of CD86 in all monocyte and DC populations after CRT. Moreover, in non-responders, the increased frequency of IL-6-producing DC persisted after CRT. Conclusion Our study provides new knowledge about the possible contribution of pDC and monocytes subsets to cardiac reverse remodelling and response to CRT. Additionally, CRT is associated with a reduction on CD86 expression by monocytes and DC subsets and in their potential to produce pro-inflammatory cytokines, contributing, at least in part, for the well described anti-inflammatory effects of CRT in HF patients.

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Reverse Remodeling in Human Heart Failure after Cardiac Resynchronization Therapy Is Associated With Reduced RHO-Kinase Activation

Cited by 3 publications

References 46 publications

New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review

New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review

Regression of cardiac hypertrophy in health and disease: mechanisms and therapeutic potential

Role of monocytes and dendritic cells in cardiac reverse remodelling after cardiac resynchronization therapy

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