HIV-Associated Hypertension: Risks, Mechanisms, and Knowledge Gaps.

HIV type 1 (HIV-1) is the causative agent of AIDS. Since the start of the epidemic, HIV/AIDS has been responsible for ≈40 million deaths. Additionally, an estimated 39 million people are currently infected with the virus. HIV-1 primarily infects immune cells, such as CD4+ (cluster of differentiation 4+) T lymphocytes (T cells), and as a consequence, the number of CD4+ T cells progressively declines in people living with HIV. Within a span of ≈10 years, HIV-1 infection leads to the systemic failure of the immune system and progression to AIDS. Fortunately, potent antiviral therapy effectively controls HIV-1 infection and prevents AIDS-related deaths. The efficacy of the current antiviral therapy regimens has transformed the outcome of HIV/AIDS from a death sentence to a chronic disease with a prolonged lifespan of people living with HIV. However, antiviral therapy is not curative, is challenged by virus resistance, can be toxic, and, most importantly, requires lifelong adherence. Furthermore, the improved lifespan has resulted in an increased incidence of non-AIDS-related morbidities in people living with HIV including cardiovascular diseases, renal disease, liver disease, bone disease, cancer, and neurological conditions. In this review, we summarize the current state of knowledge of the cardiovascular comorbidities associated with HIV-1 infection, with a particular focus on hypertension. We also discuss the potential mechanisms known to drive HIV-1-associated hypertension and the knowledge gaps in our understanding of this comorbid condition. Finally, we suggest several directions of future research to better understand the factors, pathways, and mechanisms underlying HIV-1-associated hypertension in the post-antiviral therapy era.

Functional Significance of Angiotensin Receptor Type 2 in the Neuroplasticity of Autonomic Ganglia in (mRen2)27 Transgenic Hypertensive Rats.

ABSTRACT: The over-expression of Ren -2 d gene in (mRen2)27 rats leads to development of hypertension mediated by the renin-angiotensin-system axis and exaggerated sympathetic nerve activity. Exogenously applied angiotensin II (AngII) on the superior cervical ganglion evokes ganglionic compound action potentials (gCAP) and ganglionic long-term potentiation (gLTP). We studied the functional role of angiotensin receptors and expression of reactive oxygen species marker, nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) proteins in AngII-induced postganglionic transmission. Bath-applied AngII revealed that the indices of ganglionic transmission, synaptic strength of gCAP, and decay time for gLTP are remarkably prolonged in (mRen2)27 rats and were abolished by an angiotensin receptor blocker (ARB), suggesting postganglionic AngII Type 1 (AT 1 ) receptor localization and mediation. Receptor density for AT 1 was similar in (mRen2)27 and control animals, and quantitative reverse transcription polymerase chain reaction revealed that it is consistent with the mRNA profile. Furthermore, immunocytochemistry analysis showed similar AT 1 receptor distribution and signals. However, assessment of Type 2 (AT 2 ), Ang-(1-7)-MAS and NOX4-specific proteins showed that AT 2 receptor protein expression was 4-fold lower, consistent with a low mRNA profile. MAS receptor expression was 10-fold lower and NOX4 protein was 2-fold lower. Despite similarity in the densities of AT 1 receptor, the low levels of the components of the protective arm of the renin-angiotensin system at the ganglia may contribute to the differential superior cervical ganglion sensitivity to AngII. The lower NOX4 affects reactive oxygen species balance and possibly results in activation of downstream pathways to promote increased sympathetic nerve activity. We speculate that the significant diminution in AT 2, MAS, and NOX4 protein expressions may play an indirect role in the alteration and efficacy of gCAP and gLTP in hypertension.

Redox Responsive Copolyoxalate Smart Polymers for Inflammation and Other Aging-Associated Diseases.

Polyoxalate (POx) and copolyoxalate (CPOx) smart polymers are topics of interest the field of inflammation. This is due to their drug delivery ability and their potential to target reactive oxygen species (ROS) and to accommodate small molecules such as curcumin, vanilline, and p-Hydroxybenzyl alcohol. Their biocompatibility, ultra-size tunable characteristics and bioimaging features are remarkable. In this review we discuss the genesis and concept of oxylate smart polymer-based particles and a few innovative systemic delivery methods that is designed to counteract the inflammation and other aging-associated diseases (AADs). First, we introduce the ROS and its role in human physiology. Second, we discuss the polymers and methods of incorporating small molecule in oxalate backbone and its drug delivery application. Finally, we revealed some novel proof of concepts which were proven effective in disease models and discussed the challenges of oxylate polymers.

Curcuminoids encapsulated liposome nanoparticles as a blue light emitting diode induced photodynamic therapeutic system for cancer treatment.

Unlike normal cells, cancer cells mutate to thrive in exaggerated levels of reactive oxygen species (ROS). This potentially makes them more susceptible to small molecule-induced oxidative stress. The intracellular ROS increase in cancer cells is a potential area under investigation for the development of cancer therapeutics targeting cancer cells. Visible photons of 430-490 nm wavelengths from a blue-light emitting diode (BLED) encompass the visible region of the spectrum known to induce ROS in cancer cells. Curcuminoids (CUR) naturally occurring photosensitizers sensitized by the blue wavelength of the visible light, well known for its potent anti-inflammatory and anticancer activity. Poor solubility and bioavailability, of the compound of the small molecule CUR restrict the therapeutic potential and limits CUR to be used as a photosensitizer. Here, our research group reports the use of small molecules CUR, encapsulated in liposome nanocarriers (LIP-CUR) coupled with blue light-emitting diode (BLED) induced photodynamic therapy (BLED-PDT). In A549 cancer cells in vitro, LIP-CUR coupled with BLED initiated BLED-PDT and triggered 1O2, ultimately resulting in caspase-3 activated apoptotic cell death. The combination of a non-cytotoxic dose of small molecule CUR co-treated with BLED to trigger BLED-PDT could be translated and be developed as a novel strategy for the treatment of cancer.