Nature Reviews. Cardiology

Prolonged or excessive exposure to oxidized phospholipids (OxPLs) generates chronic inflammation. OxPLs are present in atherosclerotic lesions and can be detected in plasma on apolipoprotein B (apoB)-containing lipoproteins. When initially conceptualized, OxPL-apoB measurement in plasma was expected to reflect the concentration of minimally oxidized LDL, but, surprisingly, it correlated more strongly with plasma lipoprotein(a) (Lp(a)) levels. Indeed, experimental and clinical studies show that Lp(a) particles carry the largest fraction of OxPLs among apoB-containing lipoproteins...

Suspected myocardial infarction with non-obstructive coronary arteries (MINOCA) has received increasing attention over the past decade. Given the heterogeneity in the mechanisms underlying acute myocardial infarction in the absence of obstructive coronary arteries, the syndrome of MINOCA is considered a working diagnosis that requires further investigation after diagnostic angiography studies have been performed, including coronary magnetic resonance angiography and functional angiography. Although once considered an infrequent and low-risk form of myocardial infarction, recent data have shown that the prognosis of MINOCA is not as benign as previously assumed...

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The immune system is intimately involved in the pathophysiology of heart failure. However, it is currently underused as a therapeutic target in the clinical setting. Moreover, the development of novel immunomodulatory therapies and their investigation for the treatment of patients with heart failure are hampered by the fact that currently used, evidence-based treatments for heart failure exert multiple immunomodulatory effects. In this Review, we discuss current knowledge on how evidence-based treatments for heart failure affect the immune system in addition to their primary mechanism of action, both to inform practising physicians about these pleiotropic actions and to create a framework for the development and application of future immunomodulatory therapies...

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Immune checkpoint molecules are physiological regulators of the adaptive immune response. Immune checkpoint inhibitors (ICIs), such as monoclonal antibodies targeting programmed cell death protein 1 or cytotoxic T lymphocyte-associated protein 4, have revolutionized cancer treatment and their clinical use is increasing. However, ICIs can cause various immune-related adverse events, including acute and chronic cardiotoxicity. Of these cardiovascular complications, ICI-induced acute fulminant myocarditis is the most studied, although emerging clinical and preclinical data are uncovering the importance of other ICI-related chronic cardiovascular complications, such as accelerated atherosclerosis and non-myocarditis-related heart failure...

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Timely resolution of the acute inflammatory response (or inflammation resolution) is an active, highly coordinated process that is essential to optimal health. Inflammation resolution is regulated by specific endogenous signalling molecules that function as 'stop signals' to terminate the inflammatory response when it is no longer needed; to actively promote healing, regeneration and tissue repair; and to limit pain. Specialized pro-resolving mediators are a superfamily of signalling molecules that initiate anti-inflammatory and pro-resolving actions...

Atherosclerotic plaque results from a complex interplay between lipid deposition, inflammatory changes, cell migration and arterial wall injury. Over the past two decades, clinical trials utilizing invasive arterial imaging modalities, such as intravascular ultrasonography, have shown that reducing levels of atherogenic lipoproteins, mainly serum LDL-cholesterol (LDL-C), to very low levels can safely reduce overall atherosclerotic plaque burden and favourably modify plaque composition. Classically, this outcome has been achieved with intensive statin therapy...

Non-adherence to medication is a global health problem with far-reaching individual-level and population-level consequences but remains unappreciated and under-addressed in the clinical setting. With increasing comorbidity and polypharmacy as well as an ageing population, cardiovascular disease and medication non-adherence are likely to become increasingly prevalent. Multiple methods for detecting non-adherence exist but are imperfect, and, despite emerging technology, a gold standard remains elusive. Non-adherence to medication is dynamic and often has multiple causes, particularly in the context of cardiovascular disease, which tends to require lifelong medication to control symptoms and risk factors in order to prevent disease progression...

Hypertension is a global health problem, with >1.3 billion individuals with high blood pressure worldwide. In this Review, we present an inflammatory paradigm for hypertension, emphasizing the crucial roles of immune cells, cytokines and chemokines in disease initiation and progression. T cells, monocytes, macrophages, dendritic cells, B cells and natural killer cells are all implicated in hypertension. Neoantigens, the NLRP3 inflammasome and increased sympathetic outflow, as well as cytokines (including IL-6, IL-7, IL-15, IL-18 and IL-21) and a high-salt environment, can contribute to immune activation in hypertension...

Atherosclerosis is a progressive inflammatory disorder of the arterial vessel wall characterized by substantial infiltration of macrophages, which exert both favourable and detrimental functions. Early in atherogenesis, macrophages can clear cytotoxic lipoproteins and dead cells, preventing cytotoxicity. Efferocytosis - the efficient clearance of dead cells by macrophages - is crucial for preventing secondary necrosis and stimulating the release of anti-inflammatory cytokines. In addition, macrophages can promote tissue repair and proliferation of vascular smooth muscle cells, thereby increasing plaque stability...

Cardiovascular autonomic dysfunction (CVAD) is a malfunction of the cardiovascular system caused by deranged autonomic control of circulatory homeostasis. CVAD is an important component of post-COVID-19 syndrome, also termed long COVID, and might affect one-third of highly symptomatic patients with COVID-19. The effects of CVAD can be seen at both the whole-body level, with impairment of heart rate and blood pressure control, and in specific body regions, typically manifesting as microvascular dysfunction. Many severely affected patients with long COVID meet the diagnostic criteria for two common presentations of CVAD: postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia...

Cardiac development and function are becoming increasingly well understood from different angles, including signalling, transcriptional and epigenetic mechanisms. By contrast, the importance of the post-transcriptional landscape of cardiac biology largely remains to be uncovered, building on the foundation of a few existing paradigms. The discovery during the past decade of hundreds of additional RNA-binding proteins in mammalian cells and organs, including the heart, is expected to accelerate progress and has raised intriguing possibilities for better understanding the intricacies of cardiac development, metabolism and adaptive alterations...

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