The protein and lipid composing the circulating lipoproteins finely influence their function. In particular, the anti-atherosclerotic function of high density lipoprotein (HDL), the main player in cholesterol reverse transport, is dictated by its protein mosaic, which encompasses proteins with well-established activity (ApoA1, ApoE, etc.) and proteins whose biological role remains to be fully elucidated (paraoxonase 1 and 3, glutathione peroxidase 3 etc.). It is becoming apparent that pathophysiological mechanisms, such as oxidative stress and inflammation, may perturbate the internal network of HDL (but also of other lipoproteins) leading to complete or partial loss of functionality. A relevant example of the HDL structural re-arrangement is the association with pro-inflammatory proteins, such as myeloperoxidase and serum amyloid-A, which are able to attenuate/revert the antioxidant protective action of HDL on low density lipoprotein (LDL). As a direct consequence of these changes, HDL may become dysfunctional or even proinflammatory and pro-oxidant, and thus promote atherosclerosis.
Despite recent advances in the field, the real impact of lipoprotein function in physiological and pathological conditions remains unclear. Currently, the amount of dysfunctional HDL can be only estimated by measuring the change in concentration/activity of its protein constituents or one of the biological function of the lipoprotein (e.g. promotion of cholesterol efflux from macrophages). This represents a major drawback to fully characterize HDL function and their role in health and disease. Thus, there is an urgent need to identify novel biomarkers that accurately reflect HDL functional state.
There is still a poor understanding of the nature (cause/effect) of the widely observed relationship between HDL dysfunction and cardiovascular disease (CVD). Well-designed mechanistic and epidemiological investigations could help to define the role of HDL composition/function in these disorders. It will be also important to elucidate whether these aspects may be modulated by endogenous or exogenous factors and if they may represent putative pharmacological or nutritional targets. The latter point, albeit of paramount importance from a clinical point of view, remains to be fully elucidated, with a lack of solid evidence on the effectiveness of endogen (hormones, anti- and pro-inflammatory cytokines) or dietary factors able to modulate HDL biological activity.
In this Research Topic, we aim to gather reviews and original research articles focusing on HDL functionality and regulation by endogenous and exogenous factors, including the impact of diet and food bioactive derivatives. Particularly, we welcome submission on the following topics:
• Exploring endogen and dietary modulators of the main determinants (lipid and proteins) of HDL function
• Evaluating the longitudinal pattern of protein constituents of HDL and other lipoprotein in CVD and other non-communicable diseases
• Dissecting the possible mechanism underlying the effect of dysfunctional HDL in the pathogenesis and clinical progression of CVD and other diseases
• Evaluating the mechanistic link between change in proteome and lipidome of lipid and loss of biological functions of HDL
• Identifying novel determinants of lipoprotein function and their possible role as disease biomarkers
The protein and lipid composing the circulating lipoproteins finely influence their function. In particular, the anti-atherosclerotic function of high density lipoprotein (HDL), the main player in cholesterol reverse transport, is dictated by its protein mosaic, which encompasses proteins with well-established activity (ApoA1, ApoE, etc.) and proteins whose biological role remains to be fully elucidated (paraoxonase 1 and 3, glutathione peroxidase 3 etc.). It is becoming apparent that pathophysiological mechanisms, such as oxidative stress and inflammation, may perturbate the internal network of HDL (but also of other lipoproteins) leading to complete or partial loss of functionality. A relevant example of the HDL structural re-arrangement is the association with pro-inflammatory proteins, such as myeloperoxidase and serum amyloid-A, which are able to attenuate/revert the antioxidant protective action of HDL on low density lipoprotein (LDL). As a direct consequence of these changes, HDL may become dysfunctional or even proinflammatory and pro-oxidant, and thus promote atherosclerosis.
Despite recent advances in the field, the real impact of lipoprotein function in physiological and pathological conditions remains unclear. Currently, the amount of dysfunctional HDL can be only estimated by measuring the change in concentration/activity of its protein constituents or one of the biological function of the lipoprotein (e.g. promotion of cholesterol efflux from macrophages). This represents a major drawback to fully characterize HDL function and their role in health and disease. Thus, there is an urgent need to identify novel biomarkers that accurately reflect HDL functional state.
There is still a poor understanding of the nature (cause/effect) of the widely observed relationship between HDL dysfunction and cardiovascular disease (CVD). Well-designed mechanistic and epidemiological investigations could help to define the role of HDL composition/function in these disorders. It will be also important to elucidate whether these aspects may be modulated by endogenous or exogenous factors and if they may represent putative pharmacological or nutritional targets. The latter point, albeit of paramount importance from a clinical point of view, remains to be fully elucidated, with a lack of solid evidence on the effectiveness of endogen (hormones, anti- and pro-inflammatory cytokines) or dietary factors able to modulate HDL biological activity.
In this Research Topic, we aim to gather reviews and original research articles focusing on HDL functionality and regulation by endogenous and exogenous factors, including the impact of diet and food bioactive derivatives. Particularly, we welcome submission on the following topics:
• Exploring endogen and dietary modulators of the main determinants (lipid and proteins) of HDL function
• Evaluating the longitudinal pattern of protein constituents of HDL and other lipoprotein in CVD and other non-communicable diseases
• Dissecting the possible mechanism underlying the effect of dysfunctional HDL in the pathogenesis and clinical progression of CVD and other diseases
• Evaluating the mechanistic link between change in proteome and lipidome of lipid and loss of biological functions of HDL
• Identifying novel determinants of lipoprotein function and their possible role as disease biomarkers