The Emerging Role of l-Glutamine in Cardiovascular Health and Disease

Abstract

Emerging evidence indicates that l-glutamine (Gln) plays a fundamental role in cardiovascular physiology and pathology. By serving as a substrate for the synthesis of DNA, ATP, proteins, and lipids, Gln drives critical processes in vascular cells, including proliferation, migration, apoptosis, senescence, and extracellular matrix deposition. Furthermore, Gln exerts potent antioxidant and anti-inflammatory effects in the circulation by inducing the expression of heme oxygenase-1, heat shock proteins, and glutathione. Gln also promotes cardiovascular health by serving as an l-arginine precursor to optimize nitric oxide synthesis. Importantly, Gln mitigates numerous risk factors for cardiovascular disease, such as hypertension, hyperlipidemia, glucose intolerance, obesity, and diabetes. Many studies demonstrate that Gln supplementation protects against cardiometabolic disease, ischemia-reperfusion injury, sickle cell disease, cardiac injury by inimical stimuli, and may be beneficial in patients with heart failure. However, excessive shunting of Gln to the Krebs cycle can precipitate aberrant angiogenic responses and the development of pulmonary arterial hypertension. In these instances, therapeutic targeting of the enzymes involved in glutaminolysis such as glutaminase-1, Gln synthetase, glutamate dehydrogenase, and amino acid transaminase has shown promise in preclinical models. Future translation studies employing Gln delivery approaches and/or glutaminolysis inhibitors will determine the success of targeting Gln in cardiovascular disease.

L-Glutamine Supplementation Improves the Benefits of Combined-Exercise Training on Oral Redox Balance and Inflammatory Status in Elderly Individuals

“…As aforementioned, nutritional care can also be used as a good strategy to minimize the deleterious effects of aging, not only in individuals who cannot engage into regular exercise training programs but also to promote the effects of moderate exercises in elderly subjects [14]. For instance, amino acid supplementation can act in maintenance or even increase of muscle mass, with a adjutant role in the regulation of inflammatory and antioxidant responses in the elderly population [15][16][17]. In this context, glutamine (Gln) has an essential role in the synthesis of glutathione (GSH), a renown endogenous antioxidant, and in the systemic nitrogen metabolism and transport between organs [16].…”

“…For instance, amino acid supplementation can act in maintenance or even increase of muscle mass, with a adjutant role in the regulation of inflammatory and antioxidant responses in the elderly population [15][16][17]. In this context, glutamine (Gln) has an essential role in the synthesis of glutathione (GSH), a renown endogenous antioxidant, and in the systemic nitrogen metabolism and transport between organs [16]. Furthermore, Gln may suppress the production of proinflammatory cytokines, such as TNF-α, improving the control of inflammation [18].…”

L-glutamine for sickle cell disease: Knight or pawn?

“…CO and biliverdin (and its derivative, bilirubin) have vasodilatory effects and improve vascular function by suppressing inflammation, oxidative stress, apoptosis, and vascular smooth muscle cell proliferation and migration. 52 However, glutamine can also mediate harmful angiogenic responses by fueling the Krebs cycle and stimulating the proliferation and migration of vascular cells and deposition of extracellular matrix. This could lead to vascular remodeling that is associated with conditions such as pulmonary arterial hypertension.…”

“…Glutamine is also available in more stable, dipeptide forms such L-glycyl-L-glutamine, L-arginyl-L-glutamine, and L-alanyl-L-glutamine. 52 These dipeptide forms use the high-capacity human oligopeptide transporter 1 on enterocytes, which may facilitate a higher bioavailability of the dipeptide form than free glutamine. 58 Perhaps the use of L-arginyl-L-glutamine is suitable for use in SCD where both arginine and glutamine deficiencies have been noted.…”

“…The role of glutamine in cardiometabolic disease has also been explored. 52 Metabolic profiling of large study cohorts has evaluated the glutamine-to-glutamate ratio (Gln:Glu) and its association with cardiovascular risk factors. A high Gln:Glu ratio has been positively correlated with high density lipoproteins and reduced incidence of type 2 diabetes mellitus (DM), whereas a low Gln:Glu ratio is correlated with increased body mass index (BMI), blood pressure, circulating triglycerides and insulin.…”