Adiponectin – ABC CARDIOL

ABCHF

Review Article

Heart Failure with Preserved Ejection Fraction Beyond the Myocardium: Systemic Inflammation as the Central Axis of Pathophysiology

Mylena Miki Lopes Ideta et al. Camile Miyuki Ishikawa Nihei Paulo Henrique Brites Moreira Ana Karyn Ehrenfried de Freitas

Abstract

Heart failure (HF) with preserved ejection fraction (HFpEF) is currently the most prevalent subtype of HF, particularly among older women with multiple metabolic comorbidities. Despite recent therapeutic advances, its pathophysiology remains incompletely understood and markedly heterogeneous. In 2025, Milton Packer proposed a new conceptual framework: the adipokine hypothesis. According to this hypothesis, HFpEF is a condition primarily driven by the expansion and dysfunction of visceral adipose tissue. This remodeling of adipose tissue results in altered secretion of adipokines, which are biologically active molecules with endocrine and paracrine effects on the heart, kidneys, and vascular system. The imbalance between cardioprotective and proinflammatory adipokines promotes systemic inflammation, sodium retention, volume overload, myocardial hypertrophy, and fibrosis, ultimately leading to diastolic dysfunction and exercise intolerance, which are hallmarks of HFpEF. This article reviews the main pathophysiological foundations of this hypothesis as well as the experimental and clinical evidence and therapeutic implications, which propose a unifying paradigm for understanding and managing HFpEF.

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Editorial

CTRP-3 Levels in Patients with Stable Coronary Artery Disease and Paroxysmal Atrial Fibrillation: A New Potential Biomarker in Cardiovascular Diseases

Ricardo Mourilhe-Rocha et al. Marcelo Imbroinise Bittencourt

The C1q tumor necrosis factor-related protein (CTRP) family, comprised of 15 members (CTRP1-CTRP15), is a newly discovered and highly conserved paralogue of adiponectin. Despite structural similarities between CTRP family and adiponectin, they exert pleiotropic effects on cell metabolism and have different regulation patterns.^– CTRP3 (also known as CORS-26, cartducin and cartonectin) is a member of this family. CTRP3 is a potent anti-inflammatory adipokine that inhibits proinflammatory pathways in monocytes and microcells, exerting anti-inflammatory, anti-apoptotic and cardioprotective effect during development of coronary artery disease (CAD).^– Also, this adipokine has cardioprotective properties and is inversely associated with insulin resistance parameters; its circulating levels drop in obesity and hypertension.

One of the first studies to evaluate circulating CTRP-3 and progranulin levels in patients with CAD was conducted on 362 Korean adults with acute coronary syndrome (ACS), stable angina pectoris and control subjects with various cardiometabolic risk factors. CTRP-3 concentrations were significantly decreased in patients with ACS or stable angina compared to control subjects. Correlation analysis adjusted for age and gender showed that CTRP-3 levels had a significant negative relationship with glucose and high sensitive C-reactive protein levels, and a positive relationship with HDL-cholesterol and adiponectin levels. In a multivariate logistic regression analysis, the odds ratio for CAD was 5.14 in the second tertile, and 9.04 in the first tertile of CTRP-3 levels compared to the third tertile, after adjusting for other cardiometabolic risk variables. These results suggest that CTRP-3 might be useful for assessing the risk of CAD.

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Original Article

Adiponectin Prevents Restenosis Through Inhibiting Cell Proliferation in a Rat Vein Graft Model

Yang Zhou et al. Chun Dai Bing Zhang Jianjun Ge

Abstract

Background:

Coronary artery bypass grafting (CABG) continues to be an effective therapy for coronary artery disease patients, but the vein graft is prone to restenosis or occlude. Adiponectin (ADP) is a plasma hormone protein with the function of regulating cell proliferation.

Objective:

This study used two different doses of ADP protein in a rat vein graft model to stimulate vein graft change. The aim of our study was to investigate the effect of ADP on vein graft restenosis.

Methods:

Autologous jugular veins were implanted as carotid interposition grafts through the anastomotic cuff technique in Sprague Dawley rats. Adiponectin (2.5 μg and 7.5 μg) was delivered to the vein bypass grafts in a perivascular fashion, suspended in a 30% Pluronic-F127 gel. No treatment (bypass only) and vehicle loaded Pluronic gel served as controls. Comparisons were made with one-way analysis of variance and a post-hoc test, with p < 0.05 considered significant.

Results:

Cell proliferation (PCNA index) was significantly low in adiponectin-treated versus control and vehicle-gel-treated grafts, both in intima and adventitia, as of day 3 (p < 0.01). VCAM-1 and ICAM-1 evaluated by immunohistochemistry significantly down-regulated in the adiponectin-treated vein grafts in the fourth week (p <0.01). Treatment of vein grafts with adiponectin-loaded gels reduced intimal, media, and adventitia thickness when compared with the control and vehicle-gel-treated vein grafts at day 28 (p < 0.01).

Conclusions:

Our studies provide further support for the potential therapeutic role of adiponectin in modulating vascular injury and repair.

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Original Article

Adiponectin in Relation to Coronary Plaque Characteristics on Radiofrequency Intravascular Ultrasound and Cardiovascular Outcome

Bárbara Campos Abreu Marino et al. Nermina Buljubasic Martijn Akkerhuis Jin M. Cheng … Hector M. Garcia-Garcia Evelyn Regar Robert-Jan van Geuns Patrick W. Serruys Eric Boersma Isabella Kardys

Abstract

Background:

Prospective data on the associations of adiponectin with in-vivo measurements of degree, phenotype and vulnerability of coronary atherosclerosis are currently lacking.

Objective:

To investigate the association of plasma adiponectin with virtual histology intravascular ultrasound (VH-IVUS)-derived measures of atherosclerosis and with major adverse cardiac events (MACE) in patients with established coronary artery disease.

Methods:

In 2008-2011, VH-IVUS of a non-culprit non-stenotic coronary segment was performed in 581 patients undergoing coronary angiography for acute coronary syndrome (ACS, n = 318) or stable angina pectoris (SAP, n = 263) from the atherosclerosis-intravascular ultrasound (ATHEROREMO-IVUS) study. Blood was sampled prior to coronary angiography. Coronary plaque burden, tissue composition, high-risk lesions, including VH-IVUS-derived thin-cap fibroatheroma (TCFA), were assessed. All-cause mortality, ACS, unplanned coronary revascularization were registered during a 1-year-follow-up. All statistical tests were two-tailed and p-values < 0.05 were considered statistically significant.

Results:

In the full cohort, adiponectin levels were not associated with plaque burden, nor with the various VH-tissue types. In SAP patients, adiponectin levels (median[IQR]: 2.9(1.9-3.9) µg/mL) were positively associated with VH-IVUS derived TCFA lesions, (OR[95%CI]: 1.78[1.06-3.00], p = 0.030), and inversely associated with lesions with minimal luminal area (MLA) ≤ 4.0 mm² (OR[95%CI]: 0.55[0.32-0.92], p = 0.025). In ACS patients, adiponectin levels (median[IQR]: 2.9 [1.8-4.1] µg/mL)were not associated with plaque burden, nor with tissue components. Positive association of adiponectin with death was present in the full cohort (HR[95%CI]: 2.52[1.02-6.23], p = 0.045) and (borderline) in SAP patients (HR[95%CI]: 8.48[0.92-78.0], p = 0.058). In ACS patients, this association lost statistical significance after multivariable adjustment (HR[95%CI]: 1.87[0.67-5.19], p = 0.23).

Conclusion:

In the full cohort, adiponectin levels were associated with death but not with VH-IVUS atherosclerosis measures. In SAP patients, adiponectin levels were associated with VH-IVUS-derived TCFA lesions. Altogether, substantial role for adiponectin in plaque vulnerability remains unconfirmed.

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Editorial

Adiponectin in Relation to Coronary Plaque Characteristics on Radiofrequency Intravascular Ultrasound and Cardiovascular Outcome

José Mariani Junior

Inflammation is a complex and necessary component of the response to biological, chemical, or physical stimuli, and the cellular and molecular events that initiate and regulate the interactions between the various players in the inflammatory process of the atherosclerotic lesions remain a source of ongoing investigation.

The European Collaborative Project on Inflammation and Vascular Wall Remodeling in Atherosclerosis – Intravascular Ultrasound (ATHEROREMO-IVUS) study aimed to investigate the relations of genetic profile and novel circulating and inflammatory biomarkers with coronary plaque phenotype and vulnerability as determined by intravascular ultrasound (IVUS). Results from this trial have been helping us to improve our knowledge on the role of genetic profile and circulating inflammatory biomarkers in relation to the development of atherosclerosis and vulnerable plaques.

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Artigo Original

Serum adiponectin and cardiometabolic risk in patients with acute coronary syndromes

Gustavo Bernardes de Figueiredo Oliveira et al. João Ítalo Dias França Leopoldo Soares Piegas

BACKGROUND: The adipose tissue is considered not only a storable energy source, but mainly an endocrine organ that secretes several cytokines. Adiponectin, a novel protein similar to collagen, has been found to be an adipocyte-specific cytokine and a promising cardiovascular risk marker. OBJECTIVES: To evaluate the association between serum adiponectin levels and the risk for cardiovascular events in patients with acute coronary syndromes (ACS), as well as the correlations between adiponectin and metabolic, inflammatory, and myocardial biomarkers. METHODS: We recruited 114 patients with ACS and a mean 1.13-year follow-up to measure clinical outcomes. Clinical characteristics and biomarkers were compared according to adiponectin quartiles. Cox proportional hazard regression models with Firth’s penalization were applied to assess the independent association between adiponectin and the subsequent risk for both primary (composite of cardiovascular death/non-fatal acute myocardial infarction (AMI)/non-fatal stroke) and co-primary outcomes (composite of cardiovascular death/non-fatal AMI/non-fatal stroke/rehospitalization requiring revascularization). RESULTS: There were significant direct correlations between adiponectin and age, HDL-cholesterol, and B-type natriuretic peptide (BNP), and significant inverse correlations between adiponectin and waist circumference, body weight, body mass index, Homeostasis Model Assessment (HOMA) index, triglycerides, and insulin. Adiponectin was associated with higher risk for primary and co-primary outcomes (adjusted HR 1.08 and 1.07/increment of 1000; p = 0.01 and p = 0.02, respectively). CONCLUSION: In ACS patients, serum adiponectin was an independent predictor of cardiovascular events. In addition to the anthropometric and metabolic correlations, there was a significant direct correlation between adiponectin and BNP.

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Original Article

Pulse wave velocity, blood pressure and adipocytokines in young adults: the Rio de Janeiro study

Oswaldo Luiz Pizzi et al. Andréa Araujo Brandão Roberto Pozzan Maria Eliane Campos Magalhães … Erika Maria Gonçalves Campana Flavia Lopes Fonseca Elizabete Viana de Freitas Ayrton Pires Brandão

BACKGROUND: Data on noninvasive vascular assessment and their association with cardiovascular risk variables are scarce in young individuals. OBJECTIVE: To evaluate the association between pulse wave velocity and blood pressure, anthropometric and metabolic variables, including adipocytokines, in young adults. METHODS: A total of 96 individuals aged 26 to 35 years (mean 30.09 ± 1.92; 51 males) were assessed in the Rio de Janeiro study. Pulse wave velocity (Complior method), blood pressure, body mass index, glucose, lipid profile, leptin, insulin, adiponectin and insulin resistance index (HOMA-IR) were analyzed. Subjects were stratified into three groups according to the PWV tertile for each gender. RESULTS: The group with the highest pulse wave velocity (PWV) tertile showed higher mean systolic and diastolic blood pressure, mean blood pressure, body mass index, insulin, and HOMA-IR, as well as lower mean adiponectin; higher prevalence of diabetes mellitus/glucose intolerance and hyperinsulinemia. There was a significant positive correlation of PWV with systolic blood pressure, diastolic blood pressure, pulse pressure and mean blood pressure, body mass index, and LDL-cholesterol, and a negative correlation with HDL-cholesterol and adiponectin. In the multiple regression model, after adjustment of HDL-cholesterol, LDL-cholesterol and adiponectin for gender, age, body mass index and mean blood pressure, only the male gender and mean blood pressure remained significantly correlated with PWV. CONCLUSION: PWV in young adults showed a significant association with cardiovascular risk variables, especially in the male gender, and mean blood pressure as important determinant variables. The findings suggest that PWV measurement can be useful for the identification of vascular impairment in this age group.

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Artigo Original

Influence of nutritional status and VO2max on adiponectin levels in men older than 35 years

Eduardo Camillo Martinez et al. Macos de Sá Rego Fortes Luiz Antônio dos Anjos

BACKGROUND: Adiponectin is considered an important factor in the pathogenesis of cardiovascular and metabolic diseases, due to its anti- atherogenic and anti-inflammatory properties. Few studies, however, have suggested the existence of a direct association between adiponectin levels and cardiorespiratory fitness and physical activity levels. OBJECTIVE: To verify the influence of the nutritional status and cardiorespiratory fitness on plasma adiponectin levels in adult men. METHODS: A total of 250 subjects, all in active duty in the Brazilian Army (BA), with a mean age of 42,6 ± 4,8 years volunteered to participate in the study. Plasma levels of adiponectin were measured, as well as body mass, height, waist circumference (WC), fat percentage by hydrostatic weighing and VO2max by ergospirometry. A questionnaire was used to obtain the characteristics of the physical training performed by the individuals. RESULTS: The sample showed that 121 (48%) individuals were overweight and 36 (14%) were obese. Moreover, 66 individuals (27%) had a body fat percentage > 25% and 26,7% had a WC > 94 cm. Overweight and obese individuals had significantly lower adiponectin levels than those with an adequate nutritional status. Individuals at the highest tertile of VO2max had higher adiponectin levels than the others. The adiponectin levels were positively correlated with the total weekly physical training time and VO2max and inversely correlated with body mass, BMI and WC. The correlation between adiponectin levels and VO2max did not remain significant after being adjusted for BMI and WC. CONCLUSION: Individuals with better cardiorespiratory fitness and normal nutritional status seem to present healthier levels of adiponectin.

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