Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) remain as one of the most global problematic metabolic diseases with rapidly increasing prevalence and incidence. Epidemiological studies noted that T2DM patients have by two-fold increase to develop NAFLD, and vice versa. This complex and intricate association is supported and mediated by insulin resistance (IR). In this review, we discuss the NAFLD immunopathogenesis, connection with IR and T2DM, the role of screening and noninvasive tools, and mostly the impact of the current antidiabetic drugs on steatosis liver and new potential therapeutic targets.

Hypertension as a multifactorial pathology is one of the most important cardiovascular risk factors, affecting up to 30-40% of the general population. Complex immune responses are involved in the inflammatory mechanism of hypertension, with evidence pointing to increased inflammatory mediators even in prehypertensive patients. Increased vascular permeability, thrombogenesis, and fibrosis, effects that are associated with sustained hypertension, could be attributed to chronic inflammation. Chronic inflammation triggers endothelial dysfunction via increased production of ROS through proinflammatory cytokines. Increased serum level of proinflammatory cytokines such as IL-1β, IL-6, IL-8, IL-17, IL-23, TGFβ, and TNFα in hypertensive patients has been associated with either increased blood pressure values and/or end-organ damage. Moreover, some cytokines (i.e., IL-6) seem to determine a hypertensive response to angiotensin II, regardless of blood pressure values. Understanding hypertension as an inflammatory-based pathology gives way to new therapeutic targets. As such, conventional cardiovascular drugs (statins, calcium channels blockers, and ACEIs/ARBs) have shown additional anti-inflammatory effects that could be linked to their blood pressure lowering properties. Moreover, anti-inflammatory drugs (mycophenolate mofetil) have been shown to decrease blood pressure in hypertensive patients or prevent its development in normotensive individuals. Further research is needed to evaluate whether drugs targeting hypertensive-linked proinflammatory cytokines, such as monoclonal antibodies, could become a new therapeutic option in treating arterial hypertension.

We are witnessing the globalization of a specific type of arteriosclerosis with rising prevalence, incidence and an overall cardiovascular disease burden. Currently, atherosclerosis increasingly affects the younger generation as compared to previous decades. While early preventive medicine has seen improvements, research advances in laboratory and clinical investigation promise to provide us with novel diagnosis tools. Given the physio-pathological complexity and epigenetic patterns of atherosclerosis and the discovery of new molecules involved, the therapeutic field of atherosclerosis has room for substantial growth. Thus, the scientific community is currently investigating the role of nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a crucial component of the innate immune system in different inflammatory disorders. NLRP3 is activated by distinct factors and numerous cellular and molecular events which trigger NLRP3 inflammasome assembly with subsequent cleavage of pro-interleukin (IL)-1β and pro-IL-18 pathways via caspase-1 activation, eliciting endothelial dysfunction, promotion of oxidative stress and the inflammation process of atherosclerosis. In this review, we introduce the basic cellular and molecular mechanisms of NLRP3 inflammasome activation and its role in atherosclerosis. We also emphasize its promising therapeutic pharmaceutical potential.

The incidence of heart failure with preserved ejection fraction (HFpEF) is increasing and its challenging diagnosis and management combines clinical, imagistic and biological data. Natriuretic peptides (NPs) are hormones secreted in response to myocardial stretch that, by increasing cyclic guanosine monophosphate (cGMP), counteract myocardial fibrosis and hypertrophy, increase natriuresis and determine vasodilatation. While their role in HFpEF is controversial, most authors focused on b-type natriuretic peptides (BNPs) and agreed that patients may show lower levels. In this setting, newer molecules with an increased specificity, such as middle-region pro-atrial natriuretic peptide (MR-proANP), emerged as promising markers. Augmenting NP levels, either by NP analogs or breakdown inhibition, could offer a new therapeutic target in HFpEF (already approved in their reduced EF counterparts) by increasing the deficient cGMP levels found in patients. Importantly, these peptides also retain their prognostic value. This narrative review focuses on NPs’ physiology, diagnosis, therapeutic and prognostic implication in HFpEF.

Cardiorenal syndrome encompasses complex multifactorial facets and carries significant morbidity and mortality worldwide. The bi-directional relationship between the heart and kidneys, where dysfunction in one organ worsens the function of the other, has been the leading motor for research in the last few years. In the pathophysiological process, small noncoding RNAs, epigenetics, vascular growth factors, oxidative stress, hemodynamic factors, and biomarkers play a pivotal role in the development of cardiorenal syndrome. It is therefore important to elucidate all the mechanisms in order to provide diagnostic and treatments tools. This review summarizes the hemodynamic and non-hemodynamic pathways along with biomarkers that could be the next target for diagnosis, treatment, and prognosis in cardiorenal syndrome.

Left atrial structural, functional and electrical remodelling are linked to atrial fibrillation (AF) pathophysiology and mirror the phrase “AF begets AF”. A structurally remodelled left atrium (LA) is fibrotic, dysfunctional and enlarged. Fibrosis is the hallmark of LA structural remodelling and is associated with increased risk of stroke, heart failure development and/or progression and poorer catheter ablation outcomes with increased recurrence rates. Moreover, increased atrial fibrosis has been associated with higher rates of stroke even in sinus-rhythm individuals. As such, properly assessing the fibrotic atrial cardiomyopathy in AF patients becomes necessary. In this respect, late-gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging is the gold standard in imaging myocardial fibrosis. LA structural remodelling extension offers both diagnostic and prognostic information and influences therapeutic choices. LGE-CMR scans can be used before the procedure to better select candidates and to aid in choosing the ablation technique, during the procedure (full CMR-guided ablations) and after the ablation (to assess the ablation scar). This review focuses on imaging several LA structural remodelling CMR parameters, including size, shape and fibrosis (both extension and architecture) and their impact on procedure outcomes, recurrence risk, as well as their utility in relation to the index procedure timing.