Aspirin resistance describes a phenomenon where patients receiving aspirin therapy do not respond favorably to treatment, and is categorized by continued incidence of adverse cardiovascular events and/or the lack of reduced platelet reactivity. Studies demonstrate that one in four patients with vascular disease are resistant to aspirin therapy, placing them at an almost four-fold increased risk of major adverse limb and adverse cardiovascular events. Despite the increased cardiovascular risk incurred by aspirin resistant patients, strategies to diagnose or overcome this resistance are yet to be clinically validated and integrated. Currently, five unique laboratory assays have shown promise for aspirin resistance testing: Light transmission aggregometry, Platelet Function Analyzer-100, Thromboelastography, Verify Now, and Platelet Works. Newer antiplatelet therapies such as Plavix and Ticagrelor have been tested as an alternative to overcome aspirin resistance (used both in combination with aspirin and alone) but have not proven to be superior to aspirin alone. A recent breakthrough discovery has demonstrated that rivaroxaban, an anticoagulant which functions by inhibiting active Factor X when taken in combination with aspirin, improves outcomes in patients with vascular disease. Current studies are determining how this new regime may benefit those who are considered aspirin resistant.

Fatty acid binding proteins (FABPs) are proteins found in the cytosol that contribute to disorders related to the cardiovascular system, including atherosclerosis and metabolic syndrome. Functionally, FABPs serve as intracellular lipid chaperones, interacting with hydrophobic ligands and mediating their transportation to sites of lipid metabolism. To date, nine unique members of the FABP family (FABP 1–9) have been identified and classified according to the tissue in which they are most highly expressed. In the literature, FABP3 has been shown to be a promising clinical biomarker for coronary and peripheral artery disease. Given the rising incidence of cardiovascular disease and its associated morbidity/mortality, identifying biomarkers for early diagnosis and treatment is critical. In this review, we highlight key discoveries and recent studies on the role of FABP3 in cardiovascular disorders, with a particular focus on its clinical relevance as a biomarker for peripheral artery disease.

Cardiovascular diseases (CVD) remain a global pandemic and leading cause of deaths worldwide. While several guidelines have been developed to control the development of CVDs, its prevalence keeps on increasing until this day. Cardiovascular risk factors, such as reduced exercises and high fat or glucose diets, culminate in the development of the metabolic syndrome and eventually atherosclerosis, which is driven by high blood lipid and cholesterol levels, and by endothelial dysfunction. Late complications of atherosclerosis give rise to serious clinical cardiovascular manifestations such as myocardial infarction and hypertension. Therefore, endothelial functions and the lipid metabolism play critical roles in the pathogenesis of CVDs. Fatty acid-binding proteins are a family of intracellular proteins expressed in many cell types known mainly for their interaction with and trafficking of cellular lipids. The roles of a number of isoforms in this family have been implicated in lipid metabolic homeostasis, but their influence on endothelial function and vascular homeostasis remain largely unknown. This review’s purpose is to update fundamentals about the connection between cardiovascular disease, metabolism, endothelial function, and mainly the roles of fatty acid-binding proteins.

Abdominal aortic aneurysm (AAA) is a progressive dilatation of the aorta that can lead to aortic rupture. The pathophysiology of the disease is not well characterized but is known to be caused by the general breakdown of the extracellular matrix within the aortic wall. In this comprehensive literature review, all current research on proteins that have been investigated for their potential prognostic capabilities in patients with AAA was included. A total of 45 proteins were found to be potential prognostic biomarkers for AAA, predicting incidence of AAA, AAA rupture, AAA growth, endoleak, and post-surgical mortality. The 45 proteins fell into the following seven general categories based on their primary function: (1) cardiovascular health, (2) hemostasis, (3) transport proteins, (4) inflammation and immunity, (5) kidney function, (6) cellular structure, (7) and hormones and growth factors. This is the most up-to-date literature review on current prognostic markers for AAA and their functions. This review outlines the wide pathophysiological processes that are implicated in AAA disease progression.

Peripheral arterial disease (PAD) affects more than 150 million people worldwide and is associated with high rates of lower extremity amputation, myocardial infarction, stroke and death. Fatty acid binding protein 3 (FABP3) is released into circulation in patients with skeletal muscle injury. In this pilot study, we investigated a possible association between PAD and blood levels of FABP3. Blood samples were collected from patients with clinical symptoms and diagnostic findings indicative of PAD (PAD group; ankle-brachial index [ABI] 0.9; n = 75) presenting to vascular surgery ambulatory clinics at St. Michael's Hospital. Plasma samples were analyzed by protein multiplex to quantify FABP3 levels. PAD patients were found to have higher blood levels of FABP3 compared to patients without PAD (mean 3.90 ± 1.69 vs 2.03 ± 0.78; P < .001). A subgroup analysis demonstrated that the FABP3 levels were increased by almost two-fold in patients with PAD, independent of coronary artery disease (P < .001) or diabetes mellitus status (P < .001). Moreover, a significant negative correlation between FABP3 and the ABI was observed in PAD and patients without PAD matched groups (r = –0.51; P = .001). Last, immunohistochemistry demonstrated elevated expressions of FABP3 within skeletal muscle obtained from patients with the most severe form of PAD, chronic limb-threatening ischemia, when compared with patients without PAD. Patients with PAD have elevated plasma levels of FABP3. An increasing severity of PAD is associated with higher FABP3 levels.

Peripheral artery disease (PAD) is characterized by the atherosclerotic narrowing of lower limb vessels, leading to ischemic muscle pain in older persons. Some patients experience progression to advanced chronic limb-threatening ischemia (CLTI) with poor long-term survivorship. Herein, we performed serum metabolomics to reveal the mechanisms of PAD pathophysiology that may improve its diagnosis and prognosis to CLTI complementary to the ankle–brachial index (ABI) and clinical presentations. Non-targeted metabolite profiling of serum was performed by multisegment injection–capillary electrophoresis–mass spectrometry (MSI–CE–MS) from age and sex-matched, non-diabetic, PAD participants who were recruited and clinically stratified based on the Rutherford classification into CLTI (n = 18) and intermittent claudication (IC, n = 20). Compared to the non-PAD controls (n = 20), PAD patients had lower serum concentrations of creatine, histidine, lysine, oxoproline, monomethylarginine, as well as higher circulating phenylacetylglutamine (p < 0.05). Importantly, CLTI cases exhibited higher serum concentrations of carnitine, creatinine, cystine and trimethylamine-N-oxide along with lower circulating fatty acids relative to well matched IC patients. Most serum metabolites associated with PAD progression were also correlated with ABI (r = ±0.24−0.59, p < 0.05), whereas the ratio of stearic acid to carnitine, and arginine to propionylcarnitine differentiated CLTI from IC with good accuracy (AUC = 0.87, p = 4.0 × 10⁻⁵). This work provides new biochemical insights into PAD progression for the early detection and surveillance of high-risk patients who may require peripheral vascular intervention to prevent amputation and premature death.